BRCA1 c.181T>G, p.Cys61Gly

Reasoning

The ENIGMA BRCA1 Table 9 row for BRCA1 c.181T>G / p.(Cys61Gly) pre-assigns PS3 Strong. It states that the variant alters splicing, that cDNA-based results from PMID:32546644 are not considered for code application, and that one calibrated study incorporating the mRNA splicing effect found function similar to pathogenic controls (PMID:30209399), supporting PS3. The same variant is independently tested as C61G in a cell-based homology-directed recombination assay: endogenous BRCA1 was depleted, mutant BRCA1 was used for rescue, and the C61G construct was non-functional in triplicate testing. The VCEP reserves PS3 for well-established functional studies measuring protein function alone or mRNA and protein together, and Table 9 is the governing calibrated recommendation.

VCEP rule

Well-established in vitro or in vivo functional studies supportive of a damaging effect. Apply PS3 for assays measuring effect via protein only OR mRNA and protein combined. See Specifications Table 9 for code recommendations from calibrated published assays. Also see Figure1C and Appendix E for details.

Evidence considered

• ENIGMA BRCA1 Specifications Table 9, row BRCA1 c.181T>G / p.(Cys61Gly): PS3, Strong; missense variant shown to alter splicing; cDNA-based results from PMID:32546644 are not considered for code application; one calibrated study incorporating the mRNA splicing effect found function similar to pathogenic control variants (PMID:30209399).
• ENIGMA BRCA1 Supplementary Tables, ST4 row 398: c.181T>G / p.(Cys61Gly), Functional impact - complete, LOF, score -0.26781671304; ST11 row 398 also classifies the functional impact as complete.
• Identification of breast tumor mutations in BRCA1 that abolish its function in homologous recombination (PMID:20103620), Results subsection on zinc-coordinating residues and Figure 4A: C61G was tested in a cell-based HDR rescue assay and replacement with the mutant was non-functional.
• ENIGMA BRCA1 Specifications v1.2 and Appendix E reserve PS3 for protein-function assays or combined mRNA-and-protein assays and direct users to calibrated Table 9 recommendations.

Sources

Reasoning

The variant is a missense substitution, NM_007294.4:c.181T>G (p.Cys61Gly), at amino acid 61 within the BRCA1 RING functional domain (aa 2-101). The ENIGMA rule permits PP3 for a missense variant in this domain when BayesDel no-AF predicts protein impact at the BRCA1 threshold of >=0.28. The case BayesDel no-AF score is 0.565018, and the exact variant row in Supplementary Table ST13 reports BayesDel 0.565018 in the RING domain. Therefore PP3 Supporting is met on the protein-impact path. The SpliceAI score is 0.164, below the separate PP3 splice threshold of >=0.2; that splice path is not met and is not combined with the BayesDel path. REVEL and other predictors were not used because they are not named by the governing PP3 rule. PVS1 is not applicable to this missense variant, so the ENIGMA instruction not to apply PP3 when PVS1 is met does not exclude PP3.

VCEP rule

Apply PP3 for missense or in-frame insertion, deletion or delins variants inside a (potentially) clinically important functional domain and predicted impact via protein change (BayesDel predicted Impact). ... Apply PP3 for predicted splicing (SpliceAI ≥0.2) for silent, missense/in-frame (irrespective of location in clinically important functional domain) and for intronic variants outside of the donor and acceptor ±1,2 positions. ... Missense Predictions (BayesDel no AF) ... BRCA1: ... Impact ≥0.28 ... As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA1 RING aa 2-101; BRCA1 coiled-coil aa 1391-1424; BRCA1 BRCT repeats aa 1650-1857; BRCA2 PALB2 binding domain aa 10-40; BRCA2 DNA binding aa 2481-3186.

Evidence considered

• Case normalization: NM_007294.4:c.181T>G, NP_009225.1:p.(Cys61Gly), a missense substitution at amino acid 61.
• ENIGMA Specifications v1.2, PP3 rule: missense variants inside a potentially clinically important functional domain may receive PP3 for predicted protein impact; BRCA1 BayesDel no-AF Impact threshold is >=0.28.
• ENIGMA Appendices, Table 3: BRCA1 RING domain spans amino acids 2-101 and lists C61G (c.181T>G, p.Cys61Gly) as a clinically important residue.
• Local BayesDel no-AF lookup for NM_007294.4:c.181T>G: score 0.565018.
• SupplementaryTables_V1.2_2024-11-18.xlsx, ST13 Updated Dataset Bioinf, BRCA1 c.181T>G p.Cys61Gly row: domain RING, BayesDel score 0.565018, functional category Functional impact - complete, calibration category LossOfFunction.
• SpliceAI Lookup for NM_007294.4:c.181T>G: DS_AG 0.001, DS_AL 0.147, DS_DG 0.000, DS_DL 0.164; maximum delta score 0.164, below the PP3 splice threshold of 0.2.

Sources

Reasoning

The exact BRCA1 c.181T>G row in Li et al. 2020 Supplementary Table 3 reports LOG(LR)=22.74171257019043 for 56 probands and LR=5.517121778727685e+22. The ENIGMA PP4 Very Strong threshold is LR >=350:1; explicitly, 5.517121778727685e+22 >= 350? yes. This is a clinically calibrated personal/family-history LR component governed for PP4/BP5 by the VCEP reference table.

VCEP rule

Breast cancer is very common and has a high degree of genetic heterogeneity (caused by pathogenic variants in numerous genes). Use ONLY to capture combined LR towards pathogenicity, based on multifactorial likelihood clinical data. ... PP4_Very Strong – LR ≥350:1

Evidence considered

• Li et al. 2020 Supplementary Table 3, exact row Gene=BRCA1, HGVS_Nucleotide=c.181T>G: LOG(LR)=22.74171257019043, N_Probands=56, LR=5.517121778727685e+22.
• ENIGMA PP4 Very Strong rule: LR >=350:1; explicit comparison: 5.517121778727685e+22 >= 350? yes.

Sources

Reasoning

Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic.

VCEP rule

Reputable source recently reports variant as pathogenic but the evidence is not available to the laboratory to perform an independent evaluation. ... Do not use

Evidence considered

• ENIGMA Specifications v1.2, PP5 entry: the criterion is described as a reputable source reporting the variant as pathogenic when evidence is unavailable for independent evaluation, followed by the specification 'Do not use.'
• ClinVar expert panel classification

Sources

Reasoning

The ENIGMA BRCA1 v1.2 PM2 Supporting rule requires absence from controls in the specified non-cancer gnomAD datasets, with average regional read depth >=25. The variant is observed in both required datasets: 6/236276 alleles in gnomAD v2.1 non-cancer exomes and 4/147958 alleles in gnomAD v3.1 non-cancer genomes; therefore the required absence condition is not met. The zero homozygote counts do not convert an observed allele into absence.

VCEP rule

Absent from controls in an outbred population, from gnomAD v2.1 (non-cancer, exome only subset) and gnomAD v3.1 (non-cancer). Region around the variant must have an average read depth ≥25. See Appendix G for details.

Evidence considered

• ENIGMA Specifications v1.2, Table 1/PM2: PM2 Supporting requires the variant to be absent from controls in gnomAD v2.1 non-cancer exome-only data and gnomAD v3.1 non-cancer data, with regional average read depth >=25.
• gnomAD v2.1 non-cancer exomes: variant present at 6/236276 alleles, AF 2.5394e-05, homozygotes 0.
• gnomAD v3.1 non-cancer genomes: variant present at 4/147958 alleles, AF 2.70347e-05, homozygotes 0.

Still missing

• The case evidence does not report regional average read depth, but this does not change the decision because the variant is observed rather than absent.

Sources

Reasoning

The VCEP permits PM3 only for a patient with a phenotype consistent with BRCA1-related Fanconi Anemia and co-occurrent variants in BRCA1. The governing VCEP evidence identifies a patient carrying BRCA1 c.181T>G (p.Cys61Gly) with the reduced-penetrance BRCA1 c.5096G>A (p.Arg1699Gln), with physical features and chemotherapy toxicity, but explicitly states that chromosome fragility was not present in patient-derived peripheral blood lymphocytes; the cancer occurred at age 30, not at or before 5 years. Therefore the documented observation does not satisfy either VCEP phenotype route: increased chromosome breakage plus a qualifying feature, or unknown chromosome-breakage status plus qualifying features in at least two categories. No PM3 points can be assigned from this observation.

VCEP rule

Apply for patient with phenotype consistent with BRCA1- or BRCA2-related Fanconi Anemia (FA), and co-occurrent variants in the same gene. Phenotype is considered consistent with BRCA1- or BRCA2-related FA if: (i) Increased chromosome breakage (DEB, MMC, or spontaneous) and at least one clinical feature indicative of BRCA1/2-related FA, categorized under: physical features, pathology and laboratory findings, cancer diagnosis ≤5yr. (ii) Result unknown for chromosome breakage, and at least two clinical features indicative of BRCA1/2-related FA under at least two of the three categories: physical features, pathology and laboratory findings, cancer diagnosis ≤5yr. See Table 6 for approach to assign points per proband, and final PM3 code assignment based on the sum of PM3-related points.

Evidence considered

• ClinGen ENIGMA BRCA1/2 Specifications v1.2, Table 1 PM3_VariableWeight: PM3 applies to a patient with phenotype consistent with BRCA1- or BRCA2-related Fanconi Anemia and co-occurrent variants in the same gene; the phenotype requires either increased chromosome breakage plus at least one qualifying feature, or unknown chromosome-breakage status plus at least two qualifying features in at least two categories.
• ClinGen ENIGMA BRCA1/2 Specifications v1.2, Table 6: PM3-related points are assigned for a P/LP variant in trans or homozygote, or phase unknown, only for an individual with the specified FA phenotype; final assignment is PM3_Supporting = 1 point, PM3 = 2 points, or PM3_Strong = 4 or more points.
• ClinGen ENIGMA BRCA1/2 Specifications v1.2, Appendix H, paragraph beginning 'Caveat': the patient carrying BRCA1 c.181T>G (p.Cys61Gly) and c.5096G>A (p.Arg1699Gln) had some FA features and chemotherapy toxicity, but chromosome fragility was not present in patient-derived peripheral blood lymphocytes; the breast cancer diagnosis was at age 30.
• SupplementaryTables_V1.2_2024-11-18.xlsx, matching c.181T>G / p.(Cys61Gly) row: co-occurring c.5096G>A / p.(Arg1699Gln), with Keupp 2019 and PMID:31347298 listed for the clinical observation; the row reports breast cancer at age 30 and the described physical features.

Still missing

• The VCEP record does not establish a qualifying PM3 observation with increased or unknown chromosome breakage and the required Fanconi Anemia phenotype.

Sources

Reasoning

The ENIGMA BRCA1 Table 9 row for c.181T>G / p.(Cys61Gly) assigns PS3 Strong and does not assign BS3. Its calibrated functional result is similar to pathogenic controls, while Supplementary Table ST4 classifies the variant as complete functional impact / LOF. The available functional evidence therefore supports damaging rather than no-damaging protein function, so BS3 is not met.

VCEP rule

Well-established in vitro or in vivo functional studies shows no damaging effect on protein function. Assay measures effect via protein only OR mRNA and protein combined. See Specifications Table 9 for code recommendations from calibrated published assays. Also see Figure1C and Appendix E for details.

Evidence considered

• ENIGMA BRCA1 Specifications Table 9, row BRCA1 c.181T>G / p.(Cys61Gly): PS3, Strong; the row does not provide a BS3 assignment and reports function similar to pathogenic control variants.
• ENIGMA BRCA1 Supplementary Tables, ST4 row 398: c.181T>G / p.(Cys61Gly), Functional impact - complete and LOF; ST11 row 398 likewise classifies the functional impact as complete.
• The VCEP BS3 rule requires well-established functional studies showing no damaging effect on protein function; the variant-specific calibrated result is in the opposite, damaging direction.

Sources

Reasoning

The VCEP BP1_Strong rule requires a missense variant to be outside a potentially clinically important functional domain and to have no predicted splicing effect (SpliceAI <=0.1). BRCA1 p.Cys61Gly is at residue 61 within the VCEP-defined RING domain (aa 2-101), and its case SpliceAI maximum delta is 0.164. Neither required condition is satisfied.

VCEP rule

Apply BP1_Strong for silent substitution, missense or in-frame insertion, deletion or delins variants outside a (potentially) clinically important functional domain AND no splicing predicted (SpliceAI ≤0.1). ... Missense prediction not applicable.

Evidence considered

• ENIGMA Specifications BP1_Strong rule requires the variant to be outside a potentially clinically important functional domain AND SpliceAI <=0.1; missense prediction is not applicable.
• ENIGMA Appendices Table 3/domain definition: BRCA1 RING aa 2-101; p.Cys61Gly is at residue 61.
• Case SpliceAI result for NM_007294.4:c.181T>G: maximum delta score 0.164.

Sources

Reasoning

The variant is a missense substitution inside the BRCA1 RING functional domain, so the ENIGMA BP4 missense path is applicable. That path requires both no predicted protein impact by BayesDel and no predicted splice impact by SpliceAI. The governing BRCA1 cutoffs are BayesDel no-AF <=0.15 and SpliceAI <=0.1. The observed BayesDel score is 0.565018, exceeding the benign/no-impact cutoff, and the maximum SpliceAI delta score is 0.164, also exceeding the cutoff. Neither required component is satisfied; therefore BP4 is not met. The exact variant row in Supplementary Table ST13 independently reports the RING-domain BayesDel score as 0.565018. No unlisted predictor was substituted for BayesDel or SpliceAI.

VCEP rule

Apply BP4 for: ... Missense or in-frame insertion, deletion or delins variants inside a (potentially) clinically important functional domain, and no predicted impact via protein change or splicing (BayesDel predicted No Impact AND SpliceAI ≤0.1). ... Missense Predictions (BayesDel no AF) ... BRCA1: ... No impact ≤ 0.15 ... As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA1 RING aa 2-101; BRCA1 coiled-coil aa 1391-1424; BRCA1 BRCT repeats aa 1650-1857; BRCA2 PALB2 binding domain aa 10-40; BRCA2 DNA binding aa 2481-3186.

Evidence considered

• Case normalization: NM_007294.4:c.181T>G (p.Cys61Gly), missense residue 61 in the BRCA1 RING domain aa 2-101.
• ENIGMA Specifications v1.2, BP4 rule: for a missense variant inside a potentially clinically important functional domain, both BayesDel predicted No Impact and SpliceAI <=0.1 are required; BRCA1 BayesDel No impact is <=0.15.
• Local BayesDel no-AF lookup for NM_007294.4:c.181T>G: score 0.565018, above 0.15.
• SupplementaryTables_V1.2_2024-11-18.xlsx, ST13 Updated Dataset Bioinf, BRCA1 c.181T>G p.Cys61Gly row: RING domain, BayesDel 0.565018.
• SpliceAI Lookup for NM_007294.4:c.181T>G: maximum delta score 0.164, above the BP4 cutoff of 0.1.

Sources

Reasoning

BP5 is restricted to a combined multifactorial likelihood ratio against pathogenicity. The exact Li et al. row reports LR=5.517121778727685e+22, which is in the pathogenic direction rather than the benign direction. Using the governing Supporting operator, LR <=0.48: 5.517121778727685e+22 <= 0.48? no; the Moderate, Strong, and Very Strong inequalities also fail. Therefore BP5 is not met.

VCEP rule

Use ONLY to capture combined LR against pathogenicity, based on multifactorial likelihood clinical data. ... BP5 - LR ≤0.48 to >0.23:1

Evidence considered

• Li et al. 2020 Supplementary Table 3, exact row Gene=BRCA1, HGVS_Nucleotide=c.181T>G: LOG(LR)=22.74171257019043, N_Probands=56, LR=5.517121778727685e+22.
• ENIGMA BP5 Supporting operator is LR <=0.48:1; explicit comparison: 5.517121778727685e+22 <= 0.48? no. The stricter BP5 Moderate, Strong, and Very Strong thresholds also fail.

Sources

Reasoning

The VCEP permits PS1_Moderate when a missense variant has the same amino-acid substitution as a previously established likely pathogenic variant acting through protein change, with no confirmed or predicted splicing effect (SpliceAI <=0.1). BRCA1 c.181T>A p.Cys61Ser is listed as likely pathogenic in the ENIGMA multifactorial reference data, and therefore is a same-residue, same-amino-acid comparator for c.181T>G p.Cys61Gly. However, the assessed variant has a SpliceAI maximum delta of 0.164 and the VCEP functional table describes c.181T>G as altering splicing; the available evidence does not establish that the comparator and assessed variant have the same predicted splicing event. The protein-change PS1 path is therefore unavailable, while the VCEP splicing PS1 path cannot be evaluated from the available comparator evidence.

VCEP rule

Apply PS1_Moderate, for predicted missense substitutions, where previously established likely pathogenic variant is considered to act via protein change (no confirmed or predicted effect on mRNA splicing (SpliceAI≤0.1)). ... Apply PS1_Variable Weight, for exonic and intronic variants with same predicted impact on splicing, as a previously classified (likely) pathogenic variant. Vary weight depending on relative positions, and confidence in classification of the reference variant.

Evidence considered

• ENIGMA Supplementary Tables ST7/reference variant data, row BRCA1 c.181T>A p.(Cys61Ser): (Likely) Pathogenic, posterior probability 0.95678435566, IARC class 4.
• Parsons et al. 2019 Supplementary Table 1, row BRCA1 c.181T>A p.(Cys61Ser): Combined LR 5.193279, posterior probability 0.9567843556565283, Likely Pathogenic.
• Case SpliceAI result for NM_007294.4:c.181T>G: maximum delta score 0.164, exceeding the VCEP protein-change PS1 requirement of SpliceAI <=0.1.
• ENIGMA Specifications Table 9, row BRCA1 c.181T>G p.(Cys61Gly): missense variant shown to alter splicing; calibrated functional results are reported under PS3, not PS1.

Still missing

• No VCEP-governed evidence was available establishing that c.181T>A p.Cys61Ser and c.181T>G p.Cys61Gly have the same predicted splicing event and comparable prediction strength.

Sources

Reasoning

The governing ENIGMA rule requires a case-control study with p-value <=0.05, OR >=4, and a lower confidence interval excluding 2.0. The reviewed exact-variant paper (PMID:20103620) reports a cell-based functional assay, not affected-case versus control prevalence. The literature_pass PS4 index lists additional candidate PMIDs, but the case contains no paper_extracts or fetched full text for those papers, so their abstracts/full texts could not be independently verified for exact-variant case-control counts or statistics. Therefore the PS4 rule cannot be evaluated from the available evidence.

VCEP rule

The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls. ... Case-control studies; p-value ≤0.05 and OR ≥4 (lower confidence interval excludes 2.0).

Evidence considered

• ENIGMA Specifications v1.2, PS4 rule: affected-individual prevalence must be significantly increased versus controls; case-control studies require p-value <=0.05, OR >=4, and a lower confidence interval excluding 2.0.
• PMID:20103620, Results/Figure 4A: C61G was evaluated in a cell-based HDR assay; the source does not report affected-case and control prevalence counts for the variant.
• The literature_pass PS4 candidate index was checked; no independently extracted full-text evidence for those additional candidate papers was available in this case.

Still missing

• The literature_pass.json PS4 candidate list includes PMIDs 10447273, 10788334, 11102977, 14986830, 17508274, 20065170, 20180014, 20345474, 20507347, 20569256, 26324357, 29939840, and 31479213; their exact-variant case-control evidence requires abstract/full-text verification.
• PMID:20103620 was verified and contains functional HDR data, but no case-control prevalence comparison.

Sources

Reasoning

The VCEP requires co-segregation with disease in multiple affected family members measured by a quantitative co-segregation method and assigns strength from the Bayes-score likelihood ratio. The case evidence provides no quantitative co-segregation result, family-level meioses, proband/relative genotypes, or affected-relative segregation data. The on-record HUMU-40-1557-s001.xlsx file was searched for c.181T>G, p.Cys61Gly, and p.C61G; no entry for this variant was found. The available clinical-history LR record is not used for PP1 under the governing file guidance.

VCEP rule

Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease, as measured by a quantitative co-segregation analysis method. See Appendix I for details. ... Apply weight as per Bayes Score: ... PP1 - LR ≥2.08:1 ... PP1_Moderate – LR≥4.3:1 ... PP1_Strong – LR≥18.7:1 ... PP1_Very Strong – LR≥350:1

Evidence considered

• ENIGMA BRCA1/2 VCEP Specifications v1.2, PP1 rule: co-segregation in multiple affected family members must be measured by a quantitative co-segregation method, with PP1 Supporting at LR >=2.08:1, PP1 Moderate at LR >=4.3:1, PP1 Strong at LR >=18.7:1, and PP1 Very Strong at LR >=350:1.
• The case evidence contains no quantitative PP1 co-segregation LR, Bayes score, family meioses, or affected-relative genotype/phenotype segregation dataset.
• HUMU-40-1557-s001.xlsx converted full text was searched for c.181T>G, p.Cys61Gly, and p.C61G; no matching row was found.

Still missing

• No quantitative co-segregation LR, Bayes score, or meiosis count is available for NM_007294.4:c.181T>G.
• No family-level affected-relative genotypes, phenotype details, or phase information are available.
• No entry for c.181T>G, p.Cys61Gly, or p.C61G was found in HUMU-40-1557-s001.xlsx converted full text after searching each notation.

Sources

Reasoning

The VCEP BS2 rule requires qualifying clinical or research-cohort observations of the variant in trans with a pathogenic or likely pathogenic variant, as a homozygote, or with phase unknown, together with age/cancer-history information and absence of Fanconi Anemia features sufficient to accumulate BS2 points. The available population data show zero homozygotes in both governing non-cancer datasets, and no qualifying BS2 proband-level co-occurrence or phenotype record is available in the case evidence.

VCEP rule

BS2

Evidence considered

• ENIGMA Specifications v1.2, Table 8/BS2: points require a variant in trans with a P/LP variant, as a homozygote, or phase unknown, in a presumed Fanconi-Anemia-unaffected patient meeting age or follow-up criteria; final BS2 requires 4 or more points, moderate 2 points, or supporting 1 point.
• ENIGMA Appendix H: frequency datasets are not to be used for BS2; homozygote observations in gnomAD are captured by BA1 or BS1 instead.
• gnomAD v2.1 non-cancer exomes: homozygotes = 0.
• gnomAD v3.1 non-cancer genomes: homozygotes = 0.

Still missing

• No qualifying BS2 clinical or research-cohort observation with phase, co-occurring BRCA1 pathogenic variant, age/follow-up, and Fanconi Anemia assessment was located.
• No exact c.181T>G/p.Cys61Gly/p.C61G entry was found in HUMU-40-1557-s001.xlsx; this does not indicate absence of BS2 evidence.
• No exact c.181T>G/p.Cys61Gly/p.C61G entry was found in Specifications_V1.2_2024-11-18.docx; this does not indicate absence of BS2 evidence.

Sources

Reasoning

The VCEP requires lack of segregation in affected family members measured by a quantitative co-segregation method and assigns strength from the Bayes-score likelihood ratio. The case evidence provides no quantitative non-segregation result, family-level meioses, proband/relative genotypes, or affected-relative segregation data. The on-record HUMU-40-1557-s001.xlsx file was searched for c.181T>G, p.Cys61Gly, and p.C61G; no entry for this variant was found. The available clinical-history LR record is not used for BS4 under the governing file guidance.

VCEP rule

Lack of segregation in affected members of a family, as measured by a quantitative co-segregation analysis method. See Appendix I for details. ... Apply weight as per Bayes Score: ... BS4 - LR ≤0.05:1 ... BS4_VeryStrong – LR ≤0.00285:1 ... BS4_Moderate - LR ≤0.23:1 ... BS4_Supporting - LR ≤0.48:1

Evidence considered

• ENIGMA BRCA1/2 VCEP Specifications v1.2, BS4 rule: lack of segregation in affected family members must be measured by a quantitative co-segregation method, with BS4 Supporting at LR <=0.48:1, BS4 Moderate at LR <=0.23:1, BS4 Strong at LR <=0.05:1, and BS4 Very Strong at LR <=0.00285:1.
• The case evidence contains no quantitative BS4 non-segregation LR, Bayes score, family meioses, or affected-relative genotype/phenotype segregation dataset.
• HUMU-40-1557-s001.xlsx converted full text was searched for c.181T>G, p.Cys61Gly, and p.C61G; no matching row was found.

Still missing

• No quantitative non-segregation LR, Bayes score, or meiosis count is available for NM_007294.4:c.181T>G.
• No family-level affected-relative genotypes, phenotype details, or phase information are available.
• No entry for c.181T>G, p.Cys61Gly, or p.C61G was found in HUMU-40-1557-s001.xlsx converted full text after searching each notation.

Sources