Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189520 | SCV000243163 | uncertain significance | not provided | 2012-09-20 | criteria provided, single submitter | clinical testing | p.Lys2005Arg (AAG>AGG):c.6014 A>G in exon 47 of the SPTAN1 gene (NM_001130438.1) The Lys2005Arg missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Lys2005Arg in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. Lys2005Arg alters a position in the alpha-II spectrin protein that is highly conserved and it is located in the last spectrin repeat of the protein, which is essential for dimerization and where previous pathogenic mutations have been reported (Saitsu et al., 2010). However, the amino acid substitution is conservative, as both Lysine and Arginine are positively charged amino acid residues. One in silico algorithm predicts Lys2005Arg is damaging to protein structure and/or function, although other models suggest that it likely not pathogenic. Therefore, based on the currently available information, it is unclear whether Lys2005Arg is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV001323491 | SCV001514410 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2022-05-06 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 207346). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2005 of the SPTAN1 protein (p.Lys2005Arg). This variant is present in population databases (rs754276364, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SPTAN1-related conditions. 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. 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. |
Genome- |
RCV001808518 | SCV002056768 | uncertain significance | Developmental and epileptic encephalopathy, 5 | 2021-07-15 | criteria provided, single submitter | clinical testing |