ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1881C>A (p.Phe627Leu) (rs199473039)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182034 SCV000234337 pathogenic not provided 2011-09-16 criteria provided, single submitter clinical testing The Phe627Leu mutation in the KCNH2 gene has been published previously in association with LQTS (1-3). Phe627Leu, located in the pore region of the protein, has been reported in individuals with LQTS who harbored a different nucleotide substitution which resulted in the same Phe627Leu protein change as this patient (c.1879 T>C and c.1881 C>G, respectively). Lin et al. (2008) reported a 25-week fetus with intermittent AV block due to an extremely long QT interval who harbored the Phe627Leu mutation in the KCNH2 gene, as well as a missense mutation in the SCN5A gene. Another mutation affecting the same residue (Phe627Ile) as well as neighboring residues (Val625Glu, Gly626Ala, Gly626Asp, Gly626Ser, Gly626Val, Gly628Ala, Gly628Ser, Gly628Val) have also been reported in association with LQTS, further supporting the functional importance of this residue and this region of the protein. Phe627Leu was not detected in over 400 control chromosomes reported in the literature, nor in up to 400 control chromosomes of African American and Caucasian ancestry tested at GeneDx, indicating it is not a common benign polymorphism in these populations. Therefore, the presence of the Phe627Leu mutation in the KCNH2 gene is consistent with a diagnosis of an autosomal dominant form of LQTS. The variant is found in LQT panel(s).

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