Submissions for variant NM_002439.5(MSH3):c.2838_2839dup (p.Lys947fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002435192	SCV002750465	pathogenic	Hereditary cancer-predisposing syndrome	2023-12-04	criteria provided, single submitter	clinical testing	The c.2838_2839dupTA pathogenic mutation, located in coding exon 21 of the MSH3 gene, results from a duplication of TA at nucleotide position 2838, causing a translational frameshift with a predicted alternate stop codon (p.K947Ifs*11). 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	RCV003102775	SCV003237927	pathogenic	not provided	2022-10-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys947Ilefs*11) 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). For these reasons, this variant has been classified as Pathogenic. 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).
Myriad Genetics, Inc.	RCV003458868	SCV004189184	pathogenic	Familial adenomatous polyposis 4	2023-08-31	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.