Submissions for variant NM_000251.3(MSH2):c.1883del (p.Gly628fs)

dbSNP: rs1064795127

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482381	SCV000570626	pathogenic	not provided	2016-06-10	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in MSH2 is denoted c.1883delG at the cDNA level and p.Gly628AspfsX7 (G628DfsX7) at the protein level. The normal sequence, with the base that is deleted in braces, is AAAG[G]ACAA. The deletion causes a frameshift which changes a Glycine to an Aspartic Acid at codon 628, and creates a premature stop codon at position 7 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.
Ambry Genetics	RCV000564988	SCV000669701	pathogenic	Hereditary cancer-predisposing syndrome	2020-09-24	criteria provided, single submitter	clinical testing	The c.1883delG pathogenic mutation, located in coding exon 12 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1883, causing a translational frameshift with a predicted alternate stop codon (p.G628Dfs*7). 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.
Myriad Genetics, Inc.	RCV003449213	SCV004188028	pathogenic	Lynch syndrome 1	2023-08-04	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.