ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1669G>T (p.Glu557Ter)

dbSNP: rs63751244
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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) RCV000075308 SCV000106302 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000791445 SCV000543617 pathogenic Hereditary nonpolyposis colorectal neoplasms 2018-12-01 criteria provided, single submitter clinical testing 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 to segregate with Lynch syndrome in a family (PMID: 15655560). ClinVar contains an entry for this variant (Variation ID: 89834). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu557*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002399443 SCV002709229 pathogenic Hereditary cancer-predisposing syndrome 2020-11-20 criteria provided, single submitter clinical testing The p.E557* pathogenic mutation (also known as c.1669G>T), located in coding exon 15 of the MLH1 gene, results from a G to T substitution at nucleotide position 1669. This changes the amino acid from a glutamic acid to a stop codon within coding exon 15. This variant has been reported in a family meeting Amsterdam criteria (Apessos A et al. Br J Cancer, 2005 Jan;92:396-404). 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. RCV003455990 SCV004186469 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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