ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.2351C>G (p.Thr784Ser) (rs200624920)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235887 SCV000293027 uncertain significance not provided 2015-08-10 criteria provided, single submitter clinical testing The T773S variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The T773S 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 the T773S variant is a pathogenic or a rare benign variant.
Invitae RCV000240437 SCV000299169 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2019-06-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 773 of the SCN9A protein (p.Thr773Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs200624920, ExAC 0.04%), including at least one homozygous individual. This variant has been reported in an individual affected with progressive myoclonic epilepsy (PMID: 25401298). ClinVar contains an entry for this variant (Variation ID: 245859). 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: "Possibly 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 RCV000765525 SCV000896839 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

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