ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.121G>C (p.Val41Leu) (rs199472835)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412825 SCV000490933 likely pathogenic not provided 2015-04-09 criteria provided, single submitter clinical testing While the V41L variant in theKCNH2 gene has not been reported to our knowledge, variants affecting this same residue (V41F and V41A)have been reported in association with LQTS (Kapplinger et al., 2009; Nagaoka et al., 2008). V41F has beenreported in one individual with LQTS and was absent in 2600 controls alleles and V41A has been reported inone individual of Japanese ancestry with LQTS (Kapplinger et al., 2009; Nagaoka et al., 2008). Variants innearby residues (R35W, C39R, I42N, Y43D, Y43C) have also been reported in HGMD in association withLQTS (Stenson P et al., 2014), further supporting the functional importance of this region of the protein. TheV41L variant is a conservative amino acid substitution at a position that is conserved among mammals.Furthermore, the V41L variant was not observed in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant inthese populations.Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is abenign variant cannot be excluded.

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