Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foundation for Research in Genetics and Endocrinology, |
RCV000785869 | SCV000899110 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 7 | 2019-02-01 | criteria provided, single submitter | clinical testing | The proband carried a heterozygous variant p.Asn615Ser in SCN9A gene. This variant has previously been reported in an Indian family with an autosomal dominant inheritance. The proband had multiple episodes of seizures. The variant is not reported in the 1000 genomes, but it has a minor allele frequency of 0.003% in the ExAC database. In-silico predictions of the variant are possibly damaging by PolyPhen-2 (HumDiv), damaging by MutationTaster2. In summary, the Asn615Ser variant meets our criteria to be classified as variant of uncertain significance. |
Labcorp Genetics |
RCV001216997 | SCV001388822 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2022-05-05 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 634994). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. This variant is present in population databases (rs780995899, gnomAD 0.02%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 615 of the SCN9A protein (p.Asn615Ser). |