Submissions for variant NM_000179.3(MSH6):c.1162dup (p.His388fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002321187	SCV002626251	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-14	criteria provided, single submitter	clinical testing	The c.1162dupC pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of C at nucleotide position 1162, causing a translational frameshift with a predicted alternate stop codon (p.H388Pfs*5). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003759121	SCV004485975	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2022-12-12	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: 1737242). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His388Profs*5) 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).