Submissions for variant NM_000251.2(MSH2):c.387_388delTC (rs63750924)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000076591	SCV000107624	pathogenic	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Coding sequence variation resulting in a stop codon
Invitae	RCV000684791	SCV000255276	pathogenic	Hereditary nonpolyposis colon cancer	2018-06-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln130Valfs*2) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals (PMID: 28514183, 15849733, 10375096) and several families affected with Lynch syndrome (PMID: 8592341, 12658575). This variant is also known as 129delTC or c.388_389delTC in the literature. ClinVar contains an entry for this variant (Variation ID: 91089). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000202145	SCV000292615	pathogenic	not provided	2015-09-16	criteria provided, single submitter	clinical testing	This deletion of 2 nucleotides in MSH2 is denoted c.387_388delTC at the cDNA level and p.Gln130ValfsX2 (Q130VfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is TCTC[TC]AGTT. The deletion causes a frameshift, which changes a Glutamine to a Valine at codon 130, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH2 c.387_388delTC, also known as 129delTC or c.388_389delTC using alternative nomenclature, has been observed in several individuals with personal and/or family histories consistent with Lynch syndrome (Buerstedde 1995, Wagner 2003, Mangold 2005). We consider this variant to be pathogenic.
Ambry Genetics	RCV000491648	SCV000580392	pathogenic	Hereditary cancer-predisposing syndrome	2017-09-21	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000076591	SCV000592464	pathogenic	Lynch syndrome	2012-07-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000202145	SCV000601476	pathogenic	not provided	2015-09-11	criteria provided, single submitter	clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000202145	SCV000257188	pathogenic	not provided		no assertion criteria provided	clinical testing