ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2099G>A (p.Ser700Asn) (rs794728404)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181912 SCV000234215 uncertain significance not provided 2014-07-29 criteria provided, single submitter clinical testing p.Ser1040Asn (AGC>AAC): c.3119 G>A in exon 13 of the KCNH2 gene (NM_000238.2)A variant of unknown significance has been identified in the KCNH2 gene. The S1040N variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S1040N variant was not observed in approximately 5,700 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, a missense mutation in the same residue (S1040G) has been reported in association with sudden infant death syndrome and missense mutations in nearby residues (G1036D, V1038M, D1043G, L1045F) have been reported in association with long QT syndrome, supporting the functional importance of this region of the protein. However, the S1040N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, this substitution is only moderately conserved among mammals and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s).

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