ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.184A>G (p.Ile62Val) (rs121908920)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000215091 SCV000279165 uncertain significance not provided 2016-03-22 criteria provided, single submitter clinical testing The I62V variant has been reported previously in a Hispanic patient with febrile seizures (Singh et al., 2009). The patient was a heterozygous carrier of this variant; however, family studies were not performed. The I62V variant was not identified in 276 ethnically matched control chromosomes (Singh et al., 2009). The I62V variant was not observed in approximately 6,400 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 I62V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000555200 SCV000649284 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2020-10-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 62 of the SCN9A protein (p.Ile62Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs121908920, ExAC 0.009%). This variant has been observed in an individual affected with febrile seizures (PMID: 19763161). ClinVar contains an entry for this variant (Variation ID: 6368). 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, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765531 SCV000896845 uncertain significance Primary erythromelalgia; Hereditary sensory and autonomic neuropathy type IIA; Paroxysmal extreme pain disorder; Severe myoclonic epilepsy in infancy; Indifference to pain, congenital, autosomal recessive; Generalized epilepsy with febrile seizures plus, type 7 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000006740 SCV000026932 uncertain significance Febrile seizures, familial, 3b 2009-09-01 no assertion criteria provided literature only

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