ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1201_1204del (p.Leu401fs)

dbSNP: rs1558478567
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000700856 SCV000829631 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-11-28 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: 577983). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu401Lysfs*10) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001258037 SCV001434865 pathogenic Lynch syndrome 1 2019-12-19 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 7 of the MSH2 mRNA (c.1201_1204delTTAC) causing a frameshift at codon 401. This variant leads to a premature translational stop signal (p.Leu401Lysfs*10) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). Other nearby loss-of-function variants are considered pathogenic and are associated with Lynch syndrome. In addition, a similar MSH2 variant c.1201_1202dupTT (p.Leu401PhefsTer12) has been reported as pathogenic in a 50-year-old individual with colon cancer and loss of MSH2 and MSH6 on immunohistochemistry (PMID: 26845104). Therefore, this variant is classified as pathogenic.
Myriad Genetics, Inc. RCV001258037 SCV004187042 pathogenic Lynch syndrome 1 2023-07-31 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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