ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.5588T>C (p.Met1863Thr)

dbSNP: rs201561928
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198008 SCV001368793 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3,PP4.
Invitae RCV001242219 SCV001415290 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 2022-12-30 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects SCN9A function (PMID: 29176367). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN9A protein function. ClinVar contains an entry for this variant (Variation ID: 931454). This missense change has been observed in individual(s) with painful diabetic neuropathy (PMID: 29176367). This variant is present in population databases (rs201561928, gnomAD 0.005%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1852 of the SCN9A protein (p.Met1852Thr).
GeneDx RCV001751362 SCV001985782 uncertain significance not provided 2022-08-12 criteria provided, single submitter clinical testing Identified in a patient with diabetic peripheral neuropathy in the published literature (Blesneac et al., 2018); Published functional studies demonstrate that this variant results in a gain of function (Blesneac et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29176367, 30672368)

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