ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3539C>G (p.Ser1180Ter)

dbSNP: rs766905993
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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 RCV000491840 SCV000580115 pathogenic Hereditary cancer-predisposing syndrome 2021-10-28 criteria provided, single submitter clinical testing The p.S1180* pathogenic mutation (also known as c.3539C>G), located in coding exon 6 of the MSH6 gene, results from a C to G substitution at nucleotide position 3539. This changes the amino acid from a serine to a stop codon within coding exon 6. This alteration has been reported in a glioblastoma multiforme (GBM) cancer patient from The Cancer Genome Atlas cohort (Lu C et al. Nat Commun. 2015 Dec 22;6:10086; Huang KL et al. Cell, 2018 04;173:355-370.e14). 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV002467449 SCV002762826 pathogenic Lynch syndrome 5 2022-12-09 criteria provided, single submitter research PVS1, PS4_SUP, PM2_SUP
Myriad Genetics, Inc. RCV002467449 SCV004187197 pathogenic Lynch syndrome 5 2023-08-24 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003766761 SCV004640688 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-10-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1180*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is present in population databases (rs766905993, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with glioblastoma (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 428296). For these reasons, this variant has been classified as Pathogenic.

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