Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000171060 | SCV000223624 | uncertain significance | not provided | 2017-08-02 | criteria provided, single submitter | clinical testing | The T28A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. The T28A variant is a non-conservative amino acid substitution,which is likely to impact secondary protein structure as these residues differ in polarity, charge,size and/or other properties. This substitution occurs at a position that is conserved acrossspecies, and a different missense variant at the same position (T28I) as well as a missense variantin a nearby residue (D25N) have been reported in the Human Gene Mutation Database inassociation with epilepsy (Stenson et al., 2014). In silico analysis is inconsistent in its predictionsas to whether or not the variant is damaging to the protein structure/function. Based on thecurrently available information, it is unclear whether this variant is a pathogenic variant or a rarebenign variant. |
| Invitae | RCV001350746 | SCV001545162 | uncertain significance | Brugada syndrome 5 | 2022-10-30 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 190880). This missense change has been observed in individual(s) with epilepsy and/or neurodevelopmental disorders (PMID: 29655203). This variant is present in population databases (rs786205838, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 28 of the SCN1B protein (p.Thr28Ala). |
| Ambry Genetics | RCV002426813 | SCV002679216 | uncertain significance | Cardiovascular phenotype | 2020-08-17 | criteria provided, single submitter | clinical testing | The p.T28A variant (also known as c.82A>G), located in coding exon 2 of the SCN1B gene, results from an A to G substitution at nucleotide position 82. The threonine at codon 28 is replaced by alanine, an amino acid with similar properties. In one study, this alteration was detected as a SNP in individuals with epilepsy and was not detected in controls (KlassenT et al. Cell, 2011 Jun;145:1036-48). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002485076 | SCV002791279 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Developmental and epileptic encephalopathy, 52 | 2021-09-28 | criteria provided, single submitter | clinical testing |