ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.979C>T (p.Gln327Ter)

dbSNP: rs587782087
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000531237 SCV000625212 pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-01-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln327*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with colorectal and uterine cancer (PMID: 19731080). ClinVar contains an entry for this variant (Variation ID: 455464). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002384037 SCV002694964 pathogenic Hereditary cancer-predisposing syndrome 2018-03-06 criteria provided, single submitter clinical testing The p.Q327* pathogenic mutation (also known as c.979C>T), located in coding exon 11 of the MLH1 gene, results from a C to T substitution at nucleotide position 979. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This mutation was identified in a female patient diagnosed with colorectal cancer at age 30 and 32, followed by uterine cancer at age 41. Tumor studies were not performed (Jasperson KW et al. Fam. Cancer, 2010 Jun;9:99-107). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003449531 SCV004186546 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-18 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Laboratory for Genotyping Development, RIKEN RCV003159730 SCV002758043 pathogenic Gastric cancer 2021-07-01 no assertion criteria provided research

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