ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.5876A>C (p.Asp1959Ala) (rs1060502047)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467475 SCV000548349 likely pathogenic Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2017-06-02 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with alanine at codon 1948 of the SCN9A protein (p.Asp1948Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in an individual affected intractable generalized epilepsy and static encephalopathy (Invitae database). This variant identified in the SCN9A gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 25348405). It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that has been observed to occur de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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