ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.593_594del (p.Leu197_Phe198insTer)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002355873 SCV002649917 pathogenic Hereditary cancer-predisposing syndrome 2022-05-03 criteria provided, single submitter clinical testing The c.593_594delTT pathogenic mutation, located in coding exon 4 of the MSH3 gene, results from a deletion of two nucleotides at nucleotide positions 593 to 594, causing a translational frameshift with a predicted alternate stop codon (p.F198*). This alteration was identified in a cohort of 37 patients with early onset colorectal cancer that underwent whole exome sequencing (Jongmans MCJ et al. Gastroenterology, 2022 03;162:969-974.e6). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003103248 SCV003352572 pathogenic not provided 2023-04-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1750569). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe198*) in the MSH3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH3 are known to be pathogenic (PMID: 27476653).
Myriad Genetics, Inc. RCV003458858 SCV004189153 pathogenic Familial adenomatous polyposis 4 2023-08-29 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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