ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1520C>T (p.Pro507Leu) (rs794728372)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181797 SCV000234100 uncertain significance not provided 2018-12-19 criteria provided, single submitter clinical testing The P507L variant of uncertain significance in the KCNH2 gene has previously been reported in a 19 year-old female who died suddenly in her sleep; no cardiac symptoms were noted prior to her death (Lahrouchi et al., 2017). This variant has also been identified, in the absence of additional cardiac variants, in other unrelated individuals referred for LQTS genetic testing at GeneDx. It was also found to segregate with disease in at least two affected relatives from different families tested at GeneDx. The P507L variant is not observed in large population cohorts (Lek et al., 2016). P507L is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, this variant lacks observation in a significant number of affected individuals and functional evidence, which would further clarify its pathogenicity.

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