ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.583A>T (p.Lys195Ter) (rs863225383)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216838 SCV000278462 pathogenic Hereditary cancer-predisposing syndrome 2018-07-12 criteria provided, single submitter clinical testing The p.K195* pathogenic mutation (also known as c.583A>T), located in coding exon 7 of the MLH1 gene, results from an A to T substitution at nucleotide position 583. This changes the amino acid from a lysine to a stop codon within coding exon 7. This mutation has been reported in a female diagnosed with MSI-H cancer of the cecum at age 44 that was MLH1 deficient (Hinrichsen I et al. Carcinogenesis 2015 Feb; 36(2):202-11) and in a 42 year-old with a rectal adenoma (Binder H et al. J. Pathol., 2017 Oct;243:242-254). 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.
GeneDx RCV000202144 SCV000779388 pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.583A>T at the cDNA level and p.Lys195Ter (K195X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with Lynch syndrome (Hinrichsen 2015, Binder 2017) and is considered pathogenic.
Color Health, Inc RCV000216838 SCV000908609 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000202144 SCV000257105 likely pathogenic not provided no assertion criteria provided research

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