Submissions for variant NM_000251.2(MSH2):c.376G>A (p.Gly126Ser) (rs767371843)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166502	SCV000217301	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-07	criteria provided, single submitter	clinical testing	Insufficient or conflicting evidence;Co-occurence with mutation in same gene (phase unknown)
Invitae	RCV000199020	SCV000254419	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2019-12-31	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with serine at codon 126 of the MSH2 protein (p.Gly126Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs767371843, ExAC 0.001%). This variant has been reported in individuals affected with Lynch syndrome-associated tumors (PMID: 24278394, 28449805). However, one of these individuals also carried another variant in the MSH2 gene (PMID: 24278394). ClinVar contains an entry for this variant (Variation ID: 186849). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics	RCV000515190	SCV000611401	uncertain significance	Lynch syndrome I; Turcot syndrome; Muir-Torré syndrome	2017-05-23	criteria provided, single submitter	clinical testing
Color	RCV000166502	SCV001349879	uncertain significance	Hereditary cancer-predisposing syndrome	2019-06-27	criteria provided, single submitter	clinical testing

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