Submissions for variant NM_000251.3(MSH2):c.1157dup (p.Asp386fs)

dbSNP: rs730881774

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160628	SCV000211227	pathogenic	not provided	2014-06-24	criteria provided, single submitter	clinical testing	This duplication of one nucleotide is denoted MSH2 c.1157dupA at the cDNA level and p.Asp386GlufsX3 (D386EfsX3) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CCAG[A]TCTT. The duplication causes a frameshift, which changes an Aspartic Acid to a Glutamic Acid at codon 386, and creates a premature stop codon at position 3 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002515115	SCV003524577	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2022-02-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asp386Glufs*3) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 182591). This premature translational stop signal has been observed in individual(s) with endometrial cancer (PMID: 26681312). This variant is not present in population databases (gnomAD no frequency).
Myriad Genetics, Inc.	RCV003453270	SCV004186931	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.