Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
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). |
Gene |
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) |