ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.2600G>A (p.Gly867Asp) (rs879254102)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236068 SCV000293491 likely pathogenic not provided 2015-12-01 criteria provided, single submitter clinical testing The G856D variant has been previously reported in association with small fiber neuropathy, erythomelalgia, and acromesomelia (Hoeijmakers et al., 2012; Houlden et al., 2012; Brouwer et al., 2014). It has also been reported in a patient with a history of pain, cramps, warmth and redness of the upper extremities (Goldberg et al., 2012). Functional analysis showed that G856D alters channel function leading to hyperexcitability (Estacion et al., 2015; Hoeijmakers et al., 2012). The G856D 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 G856D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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