Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000221632 | SCV000279637 | uncertain significance | not provided | 2023-06-22 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV000692363 | SCV000820181 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 427 of the SCN9A protein (p.Leu427Ser). This variant is present in population databases (rs192406412, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. ClinVar contains an entry for this variant (Variation ID: 234638). 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 with a negative predictive value of 95%. 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, |
RCV000765528 | SCV000896842 | uncertain significance | Primary erythromelalgia; Neuropathy, hereditary sensory and autonomic, type 2A; Paroxysmal extreme pain disorder; Severe myoclonic epilepsy in infancy; Channelopathy-associated congenital insensitivity to pain, autosomal recessive; Generalized epilepsy with febrile seizures plus, type 7 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001336519 | SCV001529921 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 7 | 2018-07-16 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Ambry Genetics | RCV002381753 | SCV002695199 | uncertain significance | Inborn genetic diseases | 2021-11-18 | criteria provided, single submitter | clinical testing | The p.L427S variant (also known as c.1280T>C), located in coding exon 9 of the SCN9A gene, results from a T to C substitution at nucleotide position 1280. The leucine at codon 427 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant SCN9A-related neuropathic pain syndromes; however, its contribution to the development of autosomal recessive congenital insensitivity to pain is uncertain. |