Submissions for variant NM_001365536.1(SCN9A):c.3349G>T (p.Val1117Leu)

gnomAD frequency: 0.00009  dbSNP: rs200817435

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000175172	SCV000226611	uncertain significance	not provided	2015-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000540284	SCV000649317	uncertain significance	Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1106 of the SCN9A protein (p.Val1106Leu). This variant is present in population databases (rs200817435, gnomAD 0.02%). This missense change has been observed in individual(s) with Rolandic epilepsy (PMID: 29358611). ClinVar contains an entry for this variant (Variation ID: 194737). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001198858	SCV001369853	uncertain significance	Neuropathy, hereditary sensory and autonomic, type 2A	2020-03-31	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
GeneDx	RCV000175172	SCV002044284	uncertain significance	not provided	2023-02-21	criteria provided, single submitter	clinical testing	Previously reported in a patient from a cohort of individuals with rolandic epilepsy; however additional details were not provided (Bobbili et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32707200, 32412666, 29358611)
Ambry Genetics	RCV002453614	SCV002611596	uncertain significance	Inborn genetic diseases	2022-03-22	criteria provided, single submitter	clinical testing	The p.V1106L variant (also known as c.3316G>T), located in coding exon 16 of the SCN9A gene, results from a G to T substitution at nucleotide position 3316. The valine at codon 1106 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of primary erythermalgia/small fiber neuropathy and paroxysmal extreme pain disorder (PEPD); however, its contribution to the development of congenital insensitivity to pain (CIP) and hereditary sensory autonomic neuropathy type II (HSAN2D) is uncertain.
Revvity Omics, Revvity	RCV000175172	SCV003826964	uncertain significance	not provided	2021-09-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000175172	SCV004224985	uncertain significance	not provided	2022-02-11	criteria provided, single submitter	clinical testing
Bioinformatics Core, Luxembourg Center for Systems Biomedicine	RCV000655985	SCV000588261	pathogenic	Childhood epilepsy with centrotemporal spikes	2017-01-01	no assertion criteria provided	case-control	CAADphred>15