The HFE NM_000410.4:c.193A>T (NP_000401.1:p.(Ser65Cys)) missense variant has not previously been reported in somatic cancers (COSMIC). Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.HFE encodes a cell-surface protein that helps regulate the body’s iron absorption by influencing how transferrin interacts with its receptor. Inherited changes in HFE can cause hereditary hemochromatosis, a disorder in which the body stores too much iron. HFE can also be altered in cancer, and inherited HFE changes may increase the risk of some cancers.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
No pathogenic criterion marked as applied in the recorded assessment.
No benign criterion marked as applied in the recorded assessment.
VUS: no adjudicated criteria are applied, so no generic ACMG/AMP 2015 pathogenic, likely pathogenic, benign, or likely benign combination is met.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 22,016 / 1,614,088 alleles. Recorded AF 0.0136399. Recorded homozygote count 195.
This variant is present in gnomAD v2.1 (AF= 0.01022; MAF= 1.02200%, 2891/282878 alleles, homozygotes = 24) and has highest observed frequency in the European (Finnish) population (AF= 0.0213774; MAF= 2.13774%, 537/25120 alleles, homozygotes = 9); grpmax FAF= 0.0149203.
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.549. Refer to the recorded PP3/BP4 rationale for interpretation.
9 Uncertain significance · 4 Likely benign · 2 Benign · 1 Uncertain Significance. ClinVar API review status: criteria provided, conflicting classifications.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. HFE, a transmembrane protein, is altered by mutation in various cancers. Germline HFE mutations are associated with hemochromatosis and predispose to
This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 0 met · 13 not met · 11 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
PS4 is not met because the exact-variant case-control data yield OR 1.50 with 95% CI 0.62–3.64, failing the required OR >5.0 and CI-not-including-1.0 thresholds.
PP4 and BP5 remain not assessed because case-level phenotype/family-history and alternate-molecular-basis information are unavailable.
PP5 and BP6 are not met because ClinVar has zero exact-variant expert-panel submissions and ordinary laboratory or literature-only assertions are excluded.
The variant is missense, so PP3 and BP4 are adjudicated exclusively through the REVEL path under the generic rules.
REVEL 0.549 is below the PP3 supporting cutoff and above the BP4 supporting cutoff; neither computational criterion is met.
No criteria match.
The variant is HFE p.Ser65Cys (c.193A>T). The reviewed evidence documents this exact amino-acid substitution and reports it as a common polymorphism/risk factor with mild or variable iron-overload associations, but does not identify a different nucleotide change producing p.Ser65Cys that has been established as pathogenic. Therefore the required same-amino-acid pathogenic comparator for PS1 is absent.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
Generic ACMG/AMP PS4 requires a significantly increased prevalence in affected individuals, with RR or OR >5.0 and a confidence interval that does not include 1.0. Holmström et al. (PMID:12377814) reported the exact HFE S65C variant in 14/296 patients evaluated for suspected iron overload and 8/250 healthy controls. Treating these as carrier counts, I computed the case-control odds ratio as (14×242)/(282×8)=1.50 with an approximate 95% CI of 0.62–3.64. The OR is not >5.0 and the CI includes 1.0, so PS4 is not met. The paper also reported allele-frequency enrichment in non-C282Y/non-H63D patient chromosomes (4.9% versus 1.9% in controls, p<0.05), but that result does not satisfy the specified PS4 OR and confidence-interval thresholds.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Note 1: Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
HFE p.Ser65Cys lies within an annotated MHC class I-like antigen-recognition region, but the generic PM1 requirement is a mutational hotspot or critical, well-established functional domain without benign variation. No validated HFE hotspot or critical-domain specification is present, the hotspot search was negative, and p.Ser65Cys itself is frequent in population controls (gnomAD v4.1 AF 0.0136399; gnomAD v2.1 AF 0.01022), providing benign variation at the relevant site. The available review also reports no evident effect on HFE protein structure.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
Generic PM2 requires absence from controls or an extremely low frequency. The default all-comers population sources are applicable because no governing VCEP specifies a non-cancer or exome-only source. The variant is common in gnomAD v2.1 (AF 0.01021995; grpmax FAF 0.0149203) and gnomAD v4.1 (AF 0.0136399; grpmax FAF 0.0160786), far above the generic PM2 supporting threshold of 0.0001. The gnomAD v2.1 non-cancer exome subset is also positive at AF 0.00999781, so restricting to that subset would not change the conclusion.
PM2 (supporting): <= 0.0001 — SVI recommendation to downgrade PM2 to Supporting (ClinGen SVI 2020) (PMID:25741868)
The target is HFE p.Ser65Cys. The reviewed same-residue comparator search contains no candidate alternate missense variant at residue 65 with an established pathogenic classification. The available HFE literature discusses S65C itself and other HFE residues, not a pathogenic different missense substitution at Ser65. Therefore PM5 is not met.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
PP2 requires both a low rate of benign missense variation and missense variants as a common disease mechanism. HFE has substantial benign/common missense variation: p.Ser65Cys has gnomAD v4.1 AF 0.0136399 and gnomAD v2.1 AF 0.01022, and the literature reports S65C at 1.6–5.5% on Caucasian chromosomes. Although HFE disease-associated alleles include missense variants, the low-benign-missense-variation requirement is not satisfied.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
The variant is a missense substitution, so the governing generic path is REVEL only; SpliceAI and BayesDel are not used for PP3 in this situation. REVEL is 0.549, below the generic PP3 supporting threshold of >= 0.644 (ClinGen SVI REVEL calibration, PMID:36413997), so PP3 is not met.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
Generic ACMG/AMP PP5 requires a reputable source to report the variant as pathogenic when the evidence is not available to the laboratory for independent evaluation. ClinVar has no exact-variant expert-panel classification for HFE NM_000410.4:c.193A>T (p.Ser65Cys); expert-panel submissions are zero, and the available Pathogenic entry is an OMIM literature-only submission without assertion criteria. Ordinary laboratory submissions, conflicting aggregate labels, and non-expert assertions do not qualify under the requested PP5 rule.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
Generic BA1 requires a filtering allele frequency of at least 0.05. The appropriate grpmax FAF is 0.0149203 in gnomAD v2.1 and 0.0160786 in gnomAD v4.1, both below 0.05. The Amish v4.1 popmax point estimate of 0.0263736 is based on only 24/910 alleles, below the required 2000 observed alleles for using a population frequency estimate, and is not the filtering FAF. The variant is also described in the literature as a risk factor rather than a causative HFE mutation, but the frequency does not reach the stand-alone threshold regardless.
BA1 (stand-alone): >= 0.05 — ACMG/AMP 2015 stand-alone benign allele frequency (PMID:25741868)
The variant is observed in homozygotes in population data (24 in gnomAD v2.1 and 195 in gnomAD v4.1), but this does not establish healthy adult homozygotes with full penetrance expected at an early age. HFE-related hemochromatosis is late-onset and reduced-penetrance, and the available S65C study does not provide a qualifying healthy-adult homozygote observation. Therefore the ACMG/AMP BS2 evidence requirement is not met.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
BP1 applies when primarily truncating variants are known to cause disease. The HFE disease literature instead identifies recurrent missense alleles, especially C282Y and H63D, as the principal hereditary hemochromatosis variants and discusses S65C as a missense risk allele. Thus the available evidence does not support a primarily truncating disease mechanism for HFE.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
The variant is a missense substitution, so the governing generic path is REVEL only; SpliceAI is not used for BP4 in this situation. REVEL is 0.549, above the generic BP4 supporting threshold of <= 0.29 (ClinGen SVI REVEL calibration, PMID:36413997), so BP4 is not met; the result is not a gray-zone basis for substituting SpliceAI.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
Generic ACMG/AMP BP6 requires a reputable source to report the variant as benign when the evidence is not available to the laboratory for independent evaluation. ClinVar has no exact-variant expert-panel classification for HFE NM_000410.4:c.193A>T (p.Ser65Cys); expert-panel submissions are zero. The available Benign and Likely benign assertions are single-submitter laboratory submissions, not expert-panel classifications, and therefore do not qualify for BP6 under the requested rule.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
No case-level evidence documents a patient with the disease carrying HFE NM_000410.4:c.193A>T as a de novo variant, and no maternity and paternity confirmation or absence of family history is provided. The available literature concerns population, genotype-phenotype, or family-screening observations rather than a confirmed de novo occurrence.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
The reviewed HFE S65C literature reports clinical cohorts, genotype-phenotype associations, and a review statement that the substitution has no evident effect on HFE protein structure, but it does not provide a validated, reproducible in vitro or in vivo functional assay demonstrating a damaging effect for this variant. The PS3 evidence requirement is therefore not satisfied and cannot be calibrated to any strength.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
HFE-related hemochromatosis is described as recessive, and PMID:11943417 reports 12 individuals with the target S65C variant and C282Y as compound heterozygotes; five had elevated serum iron indices and three had elevated hepatic iron. However, the extracted report does not document parental or offspring testing establishing phase, which is required by the governing rule. PMID:16132052 likewise describes S65C-associated mild iron overload when inherited with C282Y in the compound-heterozygous state but is a review and does not provide qualifying phase-testing details for these observations. Therefore PM3 cannot be assessed from the available evidence.
For recessive disorders, detected in trans with a pathogenic variant ... This requires testing of parents (or offspring) to determine phase.
No case-level evidence documents HFE NM_000410.4:c.193A>T as assumed de novo in an affected patient. The available publications do not provide a proband-parent genotype configuration supporting de novo status without parental confirmation.
Assumed de novo, but without confirmation of paternity and maternity.
The available HFE S65C literature includes relatives and family-screening observations, but it does not establish co-segregation of this variant with disease in multiple affected family members. PMID:12377814 reports six S65C-carrying relatives and two C282Y/S65C brothers with differing iron findings; PMID:11943417 reports 12 C282Y/S65C individuals, including seven with normal indices and five with elevated indices, without a qualifying multigenerational segregation analysis. Therefore PP1 cannot be applied from these data.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. ... May be used as stronger evidence with increasing segregation data.
Generic ACMG/AMP PP4 requires the patient's phenotype or family history to be highly specific for a disease with a single genetic etiology. The available evidence describes study cohorts with suspected iron overload and variable HFE S65C-associated findings, including normal indices in some carriers and mild findings in others, but it does not provide this case's phenotype or family history and does not establish a single-gene-specific phenotype for HFE S65C. A case-level phenotype and family-history assessment is required.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
The frequency component exceeds the generic default: gnomAD v4.1 grpmax FAF=0.0160786 and v2.1 grpmax FAF=0.0149203, with qualifying population allele counts above 2000 for the FAF-bearing population. However, BS1 is a disorder-specific maximum-credible-frequency judgment, not an automatic 1% rule. HFE-related hemochromatosis is late-onset/reduced-penetrance, and S65C is reported as a common risk factor rather than a fully penetrant causative allele. The case does not provide disease prevalence, penetrance, allelic heterogeneity, or other inputs needed for a defensible Whiffin maximum-credible-frequency calculation; therefore the generic default alone is insufficient.
BS1 (strong): >= 0.01 — Generic SVI default; per-gene derivation preferred (Whiffin et al. 2017) (PMID:28518168) ... the criterion is 'allele frequency is greater than expected for the disorder'
The reviewed HFE S65C literature includes clinical phenotype studies and a review statement that the substitution has no evident effect on HFE protein structure, but it does not provide a well-established in vitro or in vivo assay showing no damaging effect on protein function or splicing. The BS3 evidence requirement is therefore not satisfied and cannot be calibrated to any strength.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
No family-level dataset documents affected relatives who lack HFE NM_000410.4:c.193A>T, and no validated non-segregation analysis is available. The available family and cohort observations are insufficient to establish lack of segregation; the BS4 caveat also requires consideration of phenocopies and families with more than one pathogenic variant.
Lack of segregation in affected members of a family. ... Caveat: The presence of phenocopies for common phenotypes (i.e. cancer, epilepsy) can mimic lack of segregation among affected individuals. Also, families may have more than one pathogenic variant contributing to an autosomal dominant disorder, fu
The available evidence reports S65C with C282Y in compound-heterozygous individuals, not a cis observation. The governing BP2 rule allows a trans observation only for a fully penetrant dominant gene/disorder, whereas HFE-related hemochromatosis is described in the case literature as recessive; no cis pathogenic-variant observation for HFE c.193A>T was identified. Because the available evidence does not establish either qualifying BP2 configuration, BP2 is not assessed.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
Generic ACMG/AMP BP5 requires the variant to be found in a case with an alternate molecular basis for disease. The available HFE S65C literature describes variable iron-overload phenotypes and comparator genotypes, but does not document that this case has an alternate molecular diagnosis explaining its disease. Case-level molecular and clinical information is required.
Variant found in a case with an alternate molecular basis for disease.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_000410.4:c.193A>T in HFE is a missense substitution predicted to produce NP_000401.1:p.(Ser65Cys). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for HFE, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_000410.4:c.193A>T in HFE is a missense substitution predicted to produce NP_000401.1:p.(Ser65Cys). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for HFE, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_000410.4:c.193A>T in HFE is a missense substitution predicted to produce NP_000401.1:p.(Ser65Cys). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for HFE, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_000410.4:c.193A>T in HFE is a missense substitution predicted to produce NP_000401.1:p.(Ser65Cys). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for HFE, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in HFE, mapped onto the exon structure of NM_000410.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Amish24 / 910 | 0.026 |
| European (Finnish)1415 / 64,016 | 0.02227 hom |
| European (non-Finnish)19201 / 1,180,008 | 0.016159 hom |
| Remaining individuals679 / 62,508 | 0.0114 hom |
| Admixed American314 / 60,018 | 0.00523 hom |
| Ashkenazi Jewish89 / 29,604 | 0.003 |
| African/African American190 / 75,012 | 0.00251 hom |
| Middle Eastern6 / 6,060 | 0.00099 |
| South Asian90 / 91,080 | 0.000991 hom |
| East Asian8 / 44,872 | 0.00018 |
| European (Finnish)537 / 25,120 | 0.0219 hom |
| European (non-Finnish)1977 / 129,196 | 0.01514 hom |
| Remaining individuals72 / 7,226 | 0.011 hom |
| Admixed American173 / 35,440 | 0.0049 |
| Ashkenazi Jewish35 / 10,370 | 0.0034 |
| African/African American63 / 24,958 | 0.0025 |
| South Asian30 / 30,616 | 0.00098 |
| East Asian4 / 19,952 | 0.0002 |
This variant is present in gnomAD v4.1 (AF= 0.0136399; MAF= 1.36399%, 22016/1614088 alleles, homozygotes = 195) and has highest observed frequency in the Amish population (AF= 0.0263736; MAF= 2.63736%, 24/910 alleles, homozygotes = 0); grpmax FAF= 0.0160786.
This variant is present in gnomAD v2.1 (AF= 0.01022; MAF= 1.02200%, 2891/282878 alleles, homozygotes = 24) and has highest observed frequency in the European (Finnish) population (AF= 0.0213774; MAF= 2.13774%, 537/25120 alleles, homozygotes = 9); grpmax FAF= 0.0149203.
Not available in gnomAD-Canada v1.0.
The variant is a missense substitution, so the governing generic path is REVEL only; SpliceAI and BayesDel are not used for PP3 in this situation. REVEL is 0.549, below the generic PP3 supporting threshold of >= 0.644 (ClinGen SVI REVEL calibration, PMID:36413997), so PP3 is not met.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
The variant is a missense substitution, so the governing generic path is REVEL only; SpliceAI is not used for BP4 in this situation. REVEL is 0.549, above the generic BP4 supporting threshold of <= 0.29 (ClinGen SVI REVEL calibration, PMID:36413997), so BP4 is not met; the result is not a gray-zone basis for substituting SpliceAI.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_000410.4:c.193A>T in HFE is a missense substitution predicted to produce NP_000401.1:p.(Ser65Cys). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for HFE, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.549. BayesDel score = 0.105529.
10 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
The 193 A4T transversion, which leads to the serine 65 to cysteine substitution (S65C), displays a frequency ranging from 1.6 to 5.5% on Caucasian chromosomes. This mutation produces no evident effect on the HFE protein structure, but we and others have found that it is significantly enriched on affected chromosomes that carry neither the C282Y nor the H63D mutation. Moreover, it is associated with mild iron overload phenotypes when inherited with the predominant C282Y mutation in the compound heterozygous state. As with the H63D mutation, the S65C mutation should be considered as a risk factor rather than as a causative mutation
Haemochromatosis type 1 – HFE related; subsection ‘Other HFE genotypes related to iron overload phenotypes,’ subsection ‘S65C missense mutation,’ page 1174
Twelve individuals were compound heterozygotes for C282Y and S65C. Seven, referred for family screening, had normal serum iron indices. Five subjects had elevated serum iron indices; three of these had elevated hepatic iron and have received treatment for iron overload.
Abstract, Results; Table 1; Discussion
The HFE S65C mutation was found in 14 patients and eight controls. In controls, the S65C allele frequency was 1.6%. The S65C allele frequency was enriched in non-C282Y non-H63D chromosomes from patients (4.9%) compared with controls (1.9%) (p<0.05).
Abstract, Results; Table 2; Table 4; Table 5; Table 7
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.0136399; MAF= 1.36399%, 22016/1614088 alleles, homozygotes = 195) and has highest observed frequency in the Amish population (AF= 0.0263736; MAF= 2.63736%, 24/910 alleles, homozygotes = 0); grpmax FAF= 0.0160786.
This variant is present in gnomAD v2.1 (AF= 0.01022; MAF= 1.02200%, 2891/282878 alleles, homozygotes = 24) and has highest observed frequency in the European (Finnish) population (AF= 0.0213774; MAF= 2.13774%, 537/25120 alleles, homozygotes = 9); grpmax FAF= 0.0149203.
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar as Uncertain significance (9 clinical laboratories) and as Likely benign (4 clinical laboratories) and as Benign (2 clinical laboratories) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 11)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.549. BayesDel score = 0.105529.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. HFE, a transmembrane protein, is altered by mutation in various cancers. Germline HFE mutations are associated with hemochromatosis and predispose to
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.