ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1625dup (p.Leu542fs)

dbSNP: rs775863622
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001225828 SCV001398121 pathogenic not provided 2025-01-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu542Phefs*12) 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, 37402566). This variant is present in population databases (rs775863622, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 953524). For these reasons, this variant has been classified as Pathogenic.
Sema4, Sema4 RCV002256711 SCV002535971 likely pathogenic Hereditary cancer-predisposing syndrome 2022-01-14 criteria provided, single submitter curation
Ambry Genetics RCV002256711 SCV002704293 pathogenic Hereditary cancer-predisposing syndrome 2024-03-25 criteria provided, single submitter clinical testing The c.1625dupT pathogenic mutation, located in coding exon 11 of the MSH3 gene, results from a duplication of T at nucleotide position 1625, causing a translational frameshift with a predicted alternate stop codon (p.L542Ffs*12). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. RCV003458649 SCV004189097 pathogenic Familial adenomatous polyposis 4 2023-08-30 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV003462771 SCV004197028 likely pathogenic Endometrial carcinoma 2023-11-24 criteria provided, single submitter clinical testing
GeneDx RCV001225828 SCV005331712 likely pathogenic not provided 2023-11-13 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005036494 SCV005666188 likely pathogenic Endometrial carcinoma; Familial adenomatous polyposis 4 2024-03-19 criteria provided, single submitter clinical testing

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