ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1683C>G (p.Tyr561Ter)

dbSNP: rs63751393
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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) RCV000075312 SCV000106306 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000703498 SCV000832401 pathogenic Hereditary nonpolyposis colorectal neoplasms 2018-08-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr561*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant has been observed in an individual affected with hereditary nonpolyposis colorectal cancer (PMID: 15849733). ClinVar contains an entry for this variant (Variation ID: 89838). This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV001012704 SCV001173190 pathogenic Hereditary cancer-predisposing syndrome 2018-02-21 criteria provided, single submitter clinical testing The p.Y561* pathogenic mutation (also known as c.1683C>G), located in coding exon 15 of the MLH1 gene, results from a C to G substitution at nucleotide position 1683. This changes the amino acid from a tyrosine to a stop codon within coding exon 15. In a study of 1,721 German probands suspected of HNPCC, this mutation was detected in 1 family. (Mangold E et al. Int. J. Cancer, 2005 Sep;116:692-702). 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. RCV003451050 SCV004186350 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-21 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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