ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1556C>T (p.Thr519Ile) (rs794728396)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181875 SCV000234178 uncertain significance not provided 2017-01-30 criteria provided, single submitter clinical testing p.Thr859Ile (ACC>ATC): c.2576 C>T in exon 10 of the KCNH2 (aka HERG) gene (NM_000238.2)The Thr859Ile variant in the KCNH2 gene has not been reported as a disease-causing variant or as a benign polymorphism to our knowledge. Thr859Ile results in a non-conservative amino acid substitution of a polar Threonine with a non-polar Isoleucine at a position that is conserved across species. In silico analysis predicts Thr859Ile is probably damaging to the protein structure/function. Pathogenic variants in nearby residues (Ile858Thr, Asn861His, Asn861Ile) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. Furthermore, the Thr859Ile 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.In summary, while Thr859Ile is a good candidate for a pathogenic variant, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant.

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