Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000557785 | SCV000649287 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 641 of the SCN9A protein (p.Asn641Tyr). This variant is present in population databases (rs121908918, gnomAD 0.006%). This missense change has been observed in individual(s) with febrile seizures and seizures (PMID: 19763161, 33216760). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6366). 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%. Experimental studies have shown that this missense change affects SCN9A function (PMID: 19763161, 31372899). 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. |
| New Leaf Center | RCV000006738 | SCV001371862 | benign | Generalized epilepsy with febrile seizures plus, type 7 | 2020-07-10 | criteria provided, single submitter | case-control | We identify the p.(Asn641Tyr) in heterozygous state in 18 Amish individuals without history of generalised febrile or afebrile seizures (one individual has focal seizures), inconstant with it as a cause of a monogenic epilepsy disorder. This variant had been previously described by Singh et al 2009. |
| Ambry Genetics | RCV002408454 | SCV002721488 | uncertain significance | Inborn genetic diseases | 2022-09-08 | criteria provided, single submitter | clinical testing | The p.N641Y variant (also known as c.1921A>T), located in coding exon 11 of the SCN9A gene, results from an A to T substitution at nucleotide position 1921. The asparagine at codon 641 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| OMIM | RCV000006738 | SCV000026929 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 7 | 2009-09-01 | no assertion criteria provided | literature only | |
| Genome |
RCV001535456 | SCV001749374 | not provided | Primary erythromelalgia; Neuropathy, hereditary sensory and autonomic, type 2A; Paroxysmal extreme pain disorder; Channelopathy-associated congenital insensitivity to pain, autosomal recessive | no assertion provided | phenotyping only | Variant interpreted as Pathogenic and reported on 01-22-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |