ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1192C>T (p.Gln398Ter)

dbSNP: rs63750483
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075146 SCV000106137 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV001383026 SCV001582034 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-05-20 criteria provided, single submitter clinical testing Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Lynch syndrome (PMID: 15872200). ClinVar contains an entry for this variant (Variation ID: 89674). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln398*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002336222 SCV002640842 pathogenic Hereditary cancer-predisposing syndrome 2020-06-29 criteria provided, single submitter clinical testing The p.Q398* pathogenic mutation (also known as c.1192C>T), located in coding exon 12 of the MLH1 gene, results from a C to T substitution at nucleotide position 1192. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This variant has been reported in one male diagnosed with MSI-H rectosigmoid cancer at age 49; this tumor showed loss of PMS2 and loss of MSH6 on immunohistochemistry (IHC) (Hampel H et al. N. Engl. J. Med., 2005 May;352:1851-60). It has also been reported in one of 618 unselected Chinese individuals diagnosed with colorectal cancer undergoing a 73-gene panel test (Gong R et al. Cancer Manag Res, 2019 Apr;11:3721-3739). 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. RCV003451011 SCV004189905 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-19 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.

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