MLH1 c.232G>C, p.Glu78Gln

Reasoning

PM2_Supporting is met. The governing MLH1 VCEP rule requires an absent or extremely rare allele frequency below 0.00002 (less than 1 in 50,000 alleles) in gnomAD v4. The variant is present at total AF 1.2441e-06 (2/1,607,590 alleles), grpmax FAF 3.65e-06, and zero homozygotes, all below 0.00002; the VCEP pilot-variants table was searched under c.232G>C, p.Glu78Gln, and p.E78Q with no matching entry.

VCEP rule

Absent/extremely rare allele frequency \<0.00002 (\<1 in 50,000 alleles ) in gnomAD v4 dataset

Evidence considered

• gnomAD v4.1 reports total AF 1.2441e-06 (2/1,607,590 alleles), exome AF 1.374220988477157e-06 (2/1,455,370 alleles), grpmax FAF 3.65e-06, and homozygotes = 0.
• The governing rule requires: Absent/extremely rare allele frequency <0.00002 (<1 in 50,000 alleles) in gnomAD v4 dataset.
• VCEP-pilot-variants---MMR.xlsx, full-text conversion: no matching row for c.232G>C, p.Glu78Gln, or p.E78Q.

Still missing

• VCEP-pilot-variants---MMR.xlsx was searched for c.232G>C, p.Glu78Gln, and p.E78Q; no entry for this variant was found.

Sources

Reasoning

The variant is a missense substitution, so the VCEP's missense HCI-prior pathway applies. The governing HCI-PRIORS-MLH1 table contains the exact entry c.232G>C / p.E78Q with prior probability 0.7144. This is greater than 0.68 and no greater than 0.81, satisfying PP3 at Supporting strength. The table's pre-assigned result governs; REVEL, BayesDel, and the SpliceAI no-impact score are not used for this PP3 decision.

VCEP rule

Missense variant with HCI prior probability for pathogenicity >0.68 & ≤0.81 as per [https://hci-priors.hci.utah.edu/PRIORS](https://hci-priors.hci.utah.edu/PRIORS) OR Predicted splice defect for non-canonical splicing nucleotides using SpliceAI with delta score >= 0.2 as per Walker et al 2023.

Evidence considered

• HCI-PRIORS-MLH1.txt.txt, exact row for c.232G>C / p.E78Q: prior probability of pathogenicity = 0.7144, MAPP score = 13.2, PMID22949387 listed in the row.
• The VCEP CSPEC identifies missense HCI prior probability >0.68 and ≤0.81 as PP3 Supporting; the exact table entry is therefore applied directly.

Sources

Reasoning

BA1 is not met. The governing MLH1 VCEP rule requires a gnomAD v4 Grpmax filtering allele frequency of at least 0.001 (0.1%) and exclusion as a founder pathogenic variant. The observed gnomAD v4 grpmax FAF is 3.65e-06, far below 0.001; the VCEP pilot-variants table was searched under c.232G>C, p.Glu78Gln, and p.E78Q with no matching entry.

VCEP rule

GnomAD v4 Grpmax filtering allele frequency ≥ 0.001 (0.1%) and variant is excluded as founder pathogenic variant.

Evidence considered

• gnomAD v4.1 reports total AF 1.2441e-06 (2/1,607,590 alleles), highest South Asian AF 2.19949e-05 (2/90,930 alleles), and grpmax FAF 3.65e-06; homozygotes = 0.
• The governing rule requires: GnomAD v4 Grpmax filtering allele frequency ≥ 0.001 (0.1%) and variant is excluded as founder pathogenic variant.
• VCEP-pilot-variants---MMR.xlsx, full-text conversion: no matching row for c.232G>C, p.Glu78Gln, or p.E78Q.

Still missing

• VCEP-pilot-variants---MMR.xlsx was searched for c.232G>C, p.Glu78Gln, and p.E78Q; no entry for this variant was found.

Sources

Reasoning

BS1 is not met. The governing MLH1 VCEP rule requires a gnomAD v4 Grpmax filtering allele frequency of at least 0.0001 and less than 0.001 (0.01–0.1%), with exclusion as a founder pathogenic variant. The observed gnomAD v4 grpmax FAF is 3.65e-06, below 0.0001; the VCEP pilot-variants table was searched under c.232G>C, p.Glu78Gln, and p.E78Q with no matching entry.

VCEP rule

GnomAD v4 Grpmax filtering allele frequency ≥ 0.0001 and \< 0.001 (0.01-0.1%) and variant is excluded as founder pathogenic variant.

Evidence considered

• gnomAD v4.1 reports grpmax FAF 3.65e-06, with total AF 1.2441e-06 (2/1,607,590 alleles) and no homozygotes.
• The governing rule requires: GnomAD v4 Grpmax filtering allele frequency ≥ 0.0001 and < 0.001 (0.01-0.1%) and variant is excluded as founder pathogenic variant.
• VCEP-pilot-variants---MMR.xlsx, full-text conversion: no matching row for c.232G>C, p.Glu78Gln, or p.E78Q.

Still missing

• VCEP-pilot-variants---MMR.xlsx was searched for c.232G>C, p.Glu78Gln, and p.E78Q; no entry for this variant was found.

Sources

Reasoning

The variant is missense, so the VCEP's HCI-prior pathway is the applicable BP4 path. The exact HCI-PRIORS-MLH1 entry for c.232G>C / p.E78Q gives a pathogenicity prior of 0.7144, not less than 0.11; therefore BP4 Supporting is not met. The VCEP's alternative SpliceAI no-impact path is explicitly limited to intronic and synonymous variants and is not applicable to this missense variant.

VCEP rule

Missense variant with HCI-prior probability of pathogenicity \<0.11 as per [https://hci-priors.hci.utah.edu/PRIORS](https://hci-priors.hci.utah.edu/PRIORS) OR For intronic and synonymous variants: SpliceAI predicts no splicing impact with delta score \<= 0.1 as per Walker et al 2023

Evidence considered

• HCI-PRIORS-MLH1.txt.txt, exact row for c.232G>C / p.E78Q: prior probability of pathogenicity = 0.7144.
• SpliceAI max delta score = 0.04 is present in the case evidence, but the VCEP BP4 SpliceAI alternative applies only to intronic and synonymous variants, not this missense substitution.

Sources

Reasoning

The variant is a missense substitution, but the available VCEP-governed evidence does not identify a different nucleotide change encoding p.Glu78Gln/p.E78Q that this VCEP previously established as Pathogenic, nor a qualifying same-nucleotide splice comparison. The PM5 comparator collection found zero same-residue candidates and the ClinVar record is a single-submitter uncertain-significance record, so PS1 cannot be evaluated under the VCEP rule.

VCEP rule

A predicted missense substitution that encodes the same amino acid change with a different underlying nucleotide change previously established by this VCEP as Pathogenic (not a predicted or confirmed splice defect).

Evidence considered

• The target is NM_000249.4:c.232G>C, encoding NP_000240.1:p.(Glu78Gln)/p.(E78Q).
• The PM5 comparator collection reported total_candidates_seen=9 but same_residue_candidates=0 and expert_panel_plp_candidates=0; it identified no useful same-residue comparator.
• ClinVar variation 1789704 has one single-submitter Uncertain significance submission and no expert-panel submission, so it does not establish a qualifying VCEP Pathogenic comparator.

Still missing

• A VCEP-established Pathogenic comparator encoding p.Glu78Gln/p.E78Q through a different nucleotide change is not available in the collected evidence.

Sources

Reasoning

The VCEP provides PS2 point-based de novo evidence thresholds, but the available case evidence contains no documented proband-level de novo observation, parental testing results, confirmed maternity/paternity, or calculable de novo points for NM_000249.4:c.232G>C (p.Glu78Gln). Therefore PS2 cannot be assessed without substituting an unstated rule or assuming de novo status.

VCEP rule

≥ 4 _de novo_ points; 2-3.5 _de novo_ points; 1-1.5 _de novo_ points; 0.5 _de novo_ points

Evidence considered

• No proband-level de novo observation, parental testing result, or de novo point calculation is documented in the available case evidence for NM_000249.4:c.232G>C (p.Glu78Gln).

Still missing

• Documented proband-level de novo status
• Parental genotypes and confirmation of maternity/paternity
• VCEP-compatible de novo point calculation

Sources

Reasoning

PS3 cannot be assessed because the case materials contain no variant-specific functional assay result, functional odds, quantitative repair or expression readout, or qualifying RNA assay for MLH1 c.232G>C (p.Glu78Gln/p.E78Q). The governing VCEP rule permits PS3 Strong for calibrated functional odds >18.7, PS3 Moderate for calibrated functional odds >4.3 and <=18.7, an MMR function defect following the functional assay flowchart, or complete monoallelic expression loss <10% of wild-type with and without NMD block, and PS3 Supporting for calibrated functional odds >2.08 and <=4.3; none can be evaluated from the available evidence. The required VCEP assay documentation and flowchart were searched for c.232G>C, p.Glu78Gln, and p.E78Q, but neither contains a variant-specific entry. The only fetched paper, PMID:25394175, does not mention the variant and provides no functional assay evidence.

VCEP rule

Calibrated functional assays with functional odds for pathogenicity > 18.7 ... Calibrated functional assays with functional odds for pathogenicity >4.3 and <= 18.7 ... OR MMR function defect following functional assay flowchart* ... OR Variants with monoallelic expression: complete loss of expression (<10% of wild-type in cDNA without puromycin) of the variant allele. Full-length transcript should be analysed with and without NMD block. ... Calibrated functional odds for pathogenicity >2.08 and <= 4.3

Evidence considered

• CSPEC PS3 entries: calibrated functional odds >18.7 support Strong; >4.3 and <=18.7, an MMR function defect following the functional assay flowchart, or complete monoallelic expression loss <10% of wild-type support Moderate; calibrated functional odds >2.08 and <=4.3 support Supporting.
• Functional-assay-SVI-documentation-MMR.xlsx, sheet MMR assays: validated MLH1 assay rows and their control/threshold framework are listed, but no row identifies c.232G>C, p.Glu78Gln, or p.E78Q and no variant readout is provided.
• Functional-assay-flowchart.pdf: the missense pathway requires a calibrated functional assay or two independent concordant assays, but no variant-specific assay result is available for this case.
• Searches of the two governing VCEP files for c.232G>C, p.Glu78Gln, and p.E78Q returned no variant-specific entry.
• PMID:25394175 paper_extracts entry: the paper does not mention MLH1 c.232G>C or p.(E78Q); its quoted content concerns constitutional mismatch repair deficiency generally, not this variant or a functional assay.

Still missing

• No variant-specific calibrated functional assay result or functional odds for MLH1 c.232G>C are available.
• No variant-specific quantitative MMR repair, protein-expression, localization, cellular-activity, or qualifying RNA assay result is available.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in Functional-assay-SVI-documentation-MMR.xlsx, sheet MMR assays.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in Functional-assay-flowchart.pdf.
• PMID:25394175 was reviewed; its paper extract states that the variant is not mentioned and supplies no variant-specific functional evidence.

Sources

Reasoning

The VCEP requires co-occurrence with a known pathogenic or likely pathogenic MLH1 variant in a patient with clinical features consistent with CMMRD, and requires this variant to meet PM2_Supporting. The available evidence establishes the PM2_Supporting prerequisite because gnomAD v4.1 reports a grpmax FAF of 3.65e-06, below the VCEP threshold of 0.00002, but provides no affected-proband observation, second MLH1 variant, phase, or inheritance information. Therefore no PM3 points can be assigned and PM3 cannot be assessed.

VCEP rule

Co-occurrence with a known pathogenic/likely pathogenic sequence variant in the same gene in a patient with clinical features consistent with CMMRD as per Aronson et al 2022 - Refer to “Table for CMMRD diagnosis.pdf”. For MLH1 variants - the variant has to meet PM2\_Supporting criteria. ... Pathogenic/Likely Pathogenic _in trans_: 1.0 point; ... Pathogenic/Likely Pathogenic - phase unknown: 0.5 points ... Sum all cases with the above evidence to determine the PM3 strength.

Evidence considered

• The VCEP PM3 rule requires co-occurrence with a known pathogenic/likely pathogenic sequence variant in the same gene in a patient with clinical features consistent with CMMRD and requires the MLH1 variant to meet PM2_Supporting.
• gnomAD v4.1 reports grpmax FAF=3.65e-06 for NM_000249.4:c.232G>C, below the VCEP PM2 threshold of <0.00002; no affected proband, second MLH1 variant, phase, or inheritance observation is reported in the available case evidence.

Still missing

• Affected-proband evidence with clinical features consistent with CMMRD is unavailable.
• A known pathogenic or likely pathogenic second MLH1 variant is not documented.
• Phase or inheritance information establishing trans or phase-unknown status is unavailable.

Sources

Reasoning

No different missense variant at MLH1 residue 78 classified by this VCEP as Pathogenic or Likely Pathogenic on the protein level and not due to aberrant splicing was identified. The comparator collection reported zero same-residue candidates, so neither the Moderate nor Supporting PM5 path can be applied. The VCEP rule also requires PP3 supporting for PM5; although the case contains an HCI prior of 0.7144 consistent with the VCEP PP3-supporting interval, the required same-residue comparator is absent.

VCEP rule

Missense change at an amino acid residue where a different missense change was classified by this VCEP as Pathogenic on the protein level and not due to aberrant splicing. Only use PM5 if PP3 is supporting for the missense change. Use PM5_Supporting if other variant is Likely Pathogenic due to a missense alteration.

Evidence considered

• The PM5 comparator collection reported same_residue_candidates=0, expert_panel_plp_candidates=0, and non_expert_majority_plp_candidates=0.
• The HCI-PRIORS-MLH1 table contains the target row c.232G>C/p.E78Q with prior probability 0.7144; this lies in the VCEP PP3-supporting interval (>0.68 and <=0.81), but it does not supply the required alternate same-residue comparator.

Still missing

• A different missense variant at residue 78 with a qualifying VCEP Pathogenic or Likely Pathogenic protein-level classification is not available in the collected evidence.

Sources

Reasoning

The VCEP requires co-segregation evidence evaluated by a combined Bayes Likelihood Ratio, with supporting, moderate, or strong thresholds. The available case evidence contains no disease pedigree, affected or unaffected relative genotypes and phenotypes, meioses, or combined Bayes Likelihood Ratio for NM_000249.4:c.232G>C (p.Glu78Gln). PP1 therefore cannot be assessed.

VCEP rule

Co-segregation with disease in pedigree(s) with a combined* Bayes Likelihood Ratio >18.7 in ≥2 families; Co-segregation with disease in pedigree(s) with a combined* Bayes Likelihood Ratio >4.3 & ≤18.7; Co-segregation with disease in pedigree(s) with a combined* Bayes Likelihood Ratio >2.08 & ≤4.3

Evidence considered

• No disease pedigree, relative genotype/phenotype segregation data, informative meioses, or combined Bayes Likelihood Ratio is documented in the available case evidence for NM_000249.4:c.232G>C (p.Glu78Gln).

Still missing

• Disease pedigree and phenotype data
• Genotypes of informative affected and unaffected relatives
• Informative meioses and combined Bayes Likelihood Ratio

Sources

Reasoning

PP4 is applicable, but the available case evidence contains no patient or family phenotype, tumor MSI/IHC results, tumor counts, or MLH1 promoter-methylation results. The governing VCEP requires at least one CRC or endometrial MSI-H tumor or loss of MMR protein expression consistent with the variant location, with MLH1 promoter methylation excluded for MLH1 variants. The Table-for-CMMRD-diagnosis.pdf was searched for c.232G>C, p.Glu78Gln, and p.E78Q and had no variant-specific entry; its general CMMRD scoring table cannot supply missing case phenotype. VCEP-pilot-variants---MMR.xlsx.txt was likewise searched and had no entry for this variant.

VCEP rule

1 CRC/Endometrial MSI-H tumor using a standard panel of 5-10 markers^e or tumor genome **and/or**​ loss of MMR protein expression consistent with the variant location. MSI-H tumor with inconsistent protein expression does not meet PP4. For _MLH1_ variants, _MLH1_ promoter methylation is to be excluded in the tumor.

Evidence considered

• The VCEP PP4 Supporting rule requires 1 CRC or endometrial MSI-H tumor using a standard 5-10-marker panel or tumor genome and/or loss of MMR protein expression consistent with the variant location, with MLH1 promoter methylation excluded.
• The case evidence provides no patient phenotype, tumor MSI/IHC result, tumor count, or MLH1 promoter-methylation result.
• Table-for-CMMRD-diagnosis.pdf, including its CMMRD scoring rows, was searched for c.232G>C, p.Glu78Gln, and p.E78Q; no variant-specific row was found.
• VCEP-pilot-variants---MMR.xlsx, including its pilot classification rows, was searched for c.232G>C, p.Glu78Gln, and p.E78Q; no variant-specific row was found.

Still missing

• Patient or family phenotype and tumor records are missing, including MSI status, IHC protein expression, tumor number, and MLH1 promoter-methylation results.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in Table-for-CMMRD-diagnosis.pdf.txt.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in VCEP-pilot-variants---MMR.xlsx.txt.

Sources

Reasoning

BS2 cannot be assessed from the available evidence. The governing MLH1 VCEP rule requires confirmed co-occurrence in trans with a known pathogenic sequence variant in the same gene in a suitably aged patient and no CMMRD manifestations, with phase confirmed through parents or offspring. gnomAD reports zero homozygotes but does not provide the required individual-level co-occurrence, phase, clinical age, or CMMRD information; the VCEP pilot-variants table was searched under c.232G>C, p.Glu78Gln, and p.E78Q with no matching entry.

VCEP rule

Co-occurrence ​_in trans​_ with a known pathogenic sequence variant in the same gene in a patient with colorectal cancer after age 45 (or other LS cancer above the median age of onset for that cancer in LS^​d), and who has no previous or current evidence of clinical manifestations of CMMRD as per Aronson et al 2022 (Refer to 'Table for CMMRD diagnosis.pdf'). Confirmation of phase requires testing of parents or offspring.

Evidence considered

• The governing rule requires co-occurrence in trans with a known pathogenic sequence variant in the same gene in a patient with colorectal cancer after age 45 (or another Lynch syndrome cancer above its median age of onset), no previous or current evidence of CMMRD, and parental or offspring testing to confirm phase.
• gnomAD v4.1 reports homozygotes = 0, but this population aggregate does not establish the individual-level co-occurrence, phase, clinical age, or CMMRD conditions required by BS2.
• VCEP-pilot-variants---MMR.xlsx, full-text conversion: no matching row for c.232G>C, p.Glu78Gln, or p.E78Q.

Still missing

• Required individual-level in-trans co-occurrence with a known pathogenic MLH1 variant, confirmed phase, qualifying age, and absence of CMMRD manifestations are unavailable.
• VCEP-pilot-variants---MMR.xlsx was searched for c.232G>C, p.Glu78Gln, and p.E78Q; no entry for this variant was found.

Sources

Reasoning

BS3 cannot be assessed because the case materials contain no variant-specific proficient-function result, calibrated functional odds, protein or mRNA assay result, or synonymous/intronic RNA result for MLH1 c.232G>C (p.Glu78Gln/p.E78Q). The governing VCEP rule permits BS3 Strong for calibrated functional odds <=0.05 or qualifying synonymous/intronic RNA evidence, and BS3 Supporting for calibrated functional odds >0.05 and <=0.48 or variant-specific proficient function in protein and mRNA-based assays following the MMR functional assay flowchart; none can be evaluated from the available evidence. The required VCEP assay documentation and flowchart were searched for c.232G>C, p.Glu78Gln, and p.E78Q, but neither contains a variant-specific entry. The only fetched paper, PMID:25394175, does not mention the variant and provides no functional assay evidence.

VCEP rule

Calibrated functional assays with functional odds for Pathogenicity <= 0.05 ... OR Synonymous substitutions and intronic variants with no associated mRNA aberration (either splicing or allelic imbalance) as determined by laboratory assays conducted with nonsense-mediated decay inhibition. Whenever abnormal transcripts are identified at similar levels in controls they will be considered naturally occurring isoforms and not mRNA aberrations. ... Calibrated functional assays with functional odds for Pathogenicity >0.05 & <=0.48 ... OR Variant-specific proficient function in protein and mRNA-based lab assays as per MMR functional assay flowchart*.

Evidence considered

• CSPEC BS3 entries: calibrated functional odds <=0.05 or qualifying synonymous/intronic RNA evidence support Strong; calibrated functional odds >0.05 and <=0.48 or variant-specific proficient function in protein and mRNA-based assays following the MMR functional assay flowchart support Supporting.
• Functional-assay-SVI-documentation-MMR.xlsx, sheet MMR assays: validated MLH1 assay rows and their control/threshold framework are listed, but no row identifies c.232G>C, p.Glu78Gln, or p.E78Q and no variant readout is provided.
• Functional-assay-flowchart.pdf: the proficient-function pathway requires qualifying variant-specific assay evidence, which is not available for this case.
• Searches of the two governing VCEP files for c.232G>C, p.Glu78Gln, and p.E78Q returned no variant-specific entry.
• PMID:25394175 paper_extracts entry: the paper does not mention MLH1 c.232G>C or p.(E78Q); its quoted content concerns constitutional mismatch repair deficiency generally, not this variant or a functional assay.

Still missing

• No variant-specific calibrated functional assay result or functional odds for MLH1 c.232G>C are available.
• No variant-specific protein- or mRNA-based proficient-function result is available.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in Functional-assay-SVI-documentation-MMR.xlsx, sheet MMR assays.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in Functional-assay-flowchart.pdf.
• PMID:25394175 was reviewed; its paper extract states that the variant is not mentioned and supplies no variant-specific functional evidence.

Sources

Reasoning

The VCEP requires lack of co-segregation evaluated by a combined Bayes Likelihood Ratio, with strong evidence below 0.05 and supporting evidence above 0.05 through 0.48. The available case evidence contains no non-segregating pedigree observations, informative relative genotypes and phenotypes, or combined Bayes Likelihood Ratio for NM_000249.4:c.232G>C (p.Glu78Gln). BS4 therefore cannot be assessed.

VCEP rule

Lack of co-segregation with disease in pedigree(s) with a combined* Bayes Likelihood Ratio <0.05; Lack of co-segregation with disease in pedigree(s) with a combined* Bayes Likelihood Ratio >0.05 & ≤0.48

Evidence considered

• No non-segregation observations, informative relative genotype/phenotype data, or combined Bayes Likelihood Ratio is documented in the available case evidence for NM_000249.4:c.232G>C (p.Glu78Gln).

Still missing

• Non-segregating affected or unaffected relative observations
• Relative genotypes and phenotype ascertainment
• Combined Bayes Likelihood Ratio for lack of co-segregation

Sources

Reasoning

BP5 is applicable, but the case contains no tumor-level or patient-level evidence needed to establish an alternate molecular basis. The VCEP requires either 2 or 3 qualifying tumors for BP5 Supporting—CRC/endometrial tumors with MSS and/or no MMR-protein loss, or LS-spectrum tumors with MMR-protein loss inconsistent with MLH1 variation—or one qualifying BRAF V600E or MLH1-methylated tumor pattern. No such findings are available. The Table-for-CMMRD-diagnosis.pdf and VCEP-pilot-variants---MMR.xlsx.txt were searched for c.232G>C, p.Glu78Gln, and p.E78Q; neither contains a variant-specific entry.

VCEP rule

2 or 3 tumors: CRC/Endometrial tumors with MSS and/or no loss of MMR protein expression and/or LS spectrum tumors^d with loss of MMR protein(s) that is inconsistent with the gene demonstrating genetic variation. OR  1 BRAF V600E (Colon only)/_MLH1_ methylation (in LS spectrum tumor only) with MSI-H/_MLH1_ loss.

Evidence considered

• The VCEP BP5 Supporting rule requires 2 or 3 qualifying tumors with MSS and/or no MMR-protein loss, or LS-spectrum tumors with MMR-protein loss inconsistent with the gene demonstrating variation; alternatively it requires 1 BRAF V600E or MLH1-methylated tumor pattern.
• No qualifying tumor phenotype, MSS/MSI result, MMR-protein result, BRAF V600E result, MLH1-methylation result, or tumor count is present in the case evidence.
• Table-for-CMMRD-diagnosis.pdf and VCEP-pilot-variants---MMR.xlsx were searched for all three variant notations and contained no variant-specific entry.

Still missing

• Tumor-level evidence is missing: MSS/MSI status, MMR-protein expression, BRAF V600E status, MLH1 promoter methylation, tumor count, and tumor relationship to MLH1 variation.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in Table-for-CMMRD-diagnosis.pdf.txt.
• No entry for c.232G>C, p.Glu78Gln, or p.E78Q was found in VCEP-pilot-variants---MMR.xlsx.txt.

Sources