ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.3019C>T (p.Arg1007Cys) (rs121908910)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559164 SCV000649307 likely pathogenic Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 996 of the SCN9A protein (p.Arg996Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121908910, ExAC 0.01%). This variant has been observed in individual(s) with paroxysmal extreme pain disorder (PMID: 17145499). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6356). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000006728 SCV000026919 pathogenic Paroxysmal extreme pain disorder 2006-12-07 no assertion criteria provided literature only

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