ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1473G>T (p.Lys491Asn) (rs1064795039)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480852 SCV000570448 uncertain significance not provided 2017-02-23 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.1473G>T at the cDNA level, p.Lys491Asn (K491N) at the protein level, and results in the change of a Lysine to an Asparagine (AAG>AAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Lys491Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Lysine and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. MSH2 Lys491Asn occurs at a position that is conserved in mammals and is located in the Clamp domain and the region of interaction with MSH3 and MSH6 (Guerrette 1998, Lützen 2008, Kansikas 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether MSH2 Lys491Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000775781 SCV000910228 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-14 criteria provided, single submitter clinical testing

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