Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002312780 | SCV000847237 | uncertain significance | Inborn genetic diseases | 2016-07-22 | criteria provided, single submitter | clinical testing | The p.R7C variant (also known as c.19C>T), located in coding exon 2 of the ATP1A2 gene, results from a C to T substitution at nucleotide position 19. The arginine at codon 7 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6478 samples (12956 alleles) with coverage at this position. 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 variant remains unclear. |
Invitae | RCV000716397 | SCV001507716 | uncertain significance | Familial hemiplegic migraine | 2022-11-29 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 588060). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 7 of the ATP1A2 protein (p.Arg7Cys). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATP1A2 protein function. 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. |