ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1871T>G (p.Ile624Ser) (rs1114167870)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492007 SCV000580599 likely pathogenic Hereditary cancer-predisposing syndrome 2019-06-19 criteria provided, single submitter clinical testing The p.I624S variant (also known as c.1871T>G), located in coding exon 12 of the MSH2 gene, results from a T to G substitution at nucleotide position 1871. The isoleucine at codon 624 is replaced by serine, an amino acid with dissimilar properties. This alteration was identified in a family that met Amsterdam II criteria and the colon tumor of the proband displayed high level microsatellite instability (MSI-H) with loss of MSH2 and MSH6 on immunohistochemistry (Ambry internal data). Based on an internal structural assessment, this alteration results in disruption of the sensitive interface between the ATPase and lever domains (Warren JJ et al. Mol. Cell, 2007 May;26:579-92; Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Color Health, Inc RCV000492007 SCV001351392 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-09 criteria provided, single submitter clinical testing

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