Submissions for variant NM_000251.3(MSH2):c.1090G>T (p.Glu364Ter)

dbSNP: rs1558478136

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001186447	SCV001352850	pathogenic	Hereditary cancer-predisposing syndrome	2020-02-18	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 7 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV001186447	SCV002734214	pathogenic	Hereditary cancer-predisposing syndrome	2019-06-07	criteria provided, single submitter	clinical testing	The p.E364* pathogenic mutation (also known as c.1090G>T), located in coding exon 7 of the MSH2 gene, results from a G to T substitution at nucleotide position 1090. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. This variant has been reported in one Italian Lynch syndrome family and was reported as Glu363Stop (c.1089G>T) (Lastella P et al. Fam. Cancer, 2011 Jun;10:285-95). 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.
Invitae	RCV002559937	SCV003524638	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2022-10-04	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: 924855). This variant is also known as p.Glu363Stop. This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 21286823). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu364*) 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).
Myriad Genetics, Inc.	RCV003449608	SCV004187013	pathogenic	Lynch syndrome 1	2023-07-31	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.