ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2450C>T (p.Pro817Leu) (rs143167166)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181918 SCV000234221 uncertain significance not provided 2015-11-04 criteria provided, single submitter clinical testing The P1157L variant was reported in one case of sudden infant death and was absent from 1,500 reference alleles from healthy controls (Tester et al. 2005). Additionally, the P1157L variant was not observed with any significant frequency in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P1157L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, immunoblot analysis of transiently transfected HEK293 cells revealed that P1157L, located in the distal c-terminus, demonstrated protein trafficking to the cell membrane similar to wildtype (Anderson et al., 2014). Nevertheless, a missense variant in a nearby residue (H1153Y) has been reported in the Human Gene Mutation Database in association with arrhythmia (Stenson et al., 2014).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058228 SCV000089748 not provided SUDDEN INFANT DEATH SYNDROME no assertion provided literature only This variant has been reported as associated with Sudden infant death syndrome in the following publications (PMID:15913580). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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