ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.136G>A (p.Asp46Asn) (rs794728408)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181928 SCV000234231 likely pathogenic not provided 2015-03-09 criteria provided, single submitter clinical testing The D46N variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D46N variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D46N 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. Missense mutations in nearby residues (I42N Y43D, Y42C, C44Y C44F, C44W, N45D, N45Y, N45S, G47V, G47D, C49Y, E50D) have been reported in association with LQTS, supporting the functional importance of this region of the protein.Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in LQT panel(s).

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