Submissions for variant NM_000251.3(MSH2):c.2079T>A (p.Cys693Ter)

dbSNP: rs1553369089

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657674	SCV000779423	pathogenic	not provided	2016-03-03	criteria provided, single submitter	clinical testing	This variant is denoted MSH2 c.2079T>A at the cDNA level and p.Cys693Ter (C693X) at the protein level. The substitution creates a nonsense variant, which changes a Cysteine to a premature stop codon (TGT>TGA) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Ambry Genetics	RCV002422440	SCV002727758	pathogenic	Hereditary cancer-predisposing syndrome	2022-06-29	criteria provided, single submitter	clinical testing	The p.C693* pathogenic mutation (also known as c.2079T>A), located in coding exon 13 of the MSH2 gene, results from a T to A substitution at nucleotide position 2079. This changes the amino acid from a cysteine to a stop codon within coding exon 13. 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.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000657674	SCV005199182	pathogenic	not provided	2022-06-15	criteria provided, single submitter	clinical testing