Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520358 | SCV000617440 | pathogenic | not provided | 2022-11-16 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on sodium-potassium pump function (Tavraz et al., 2008; Jen et al., 2007); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17435187, 21908445, 18451712, 22940869, 22067897, 18184292, 29486580, 28445178, 16088919, 24498617, 18728015) |
Invitae | RCV001385316 | SCV001585131 | pathogenic | Familial hemiplegic migraine | 2023-04-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 18728015). 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 expected to disrupt ATP1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 449379). This missense change has been observed in individuals with autosomal dominant familial hemiplegic migraine (PMID: 16088919, 24498617). It has also been observed to segregate with disease in related individuals. 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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 606 of the ATP1A2 protein (p.Ala606Thr). |
Preventiongenetics, |
RCV003419903 | SCV004109633 | pathogenic | ATP1A2-related condition | 2023-06-28 | criteria provided, single submitter | clinical testing | The ATP1A2 c.1816G>A variant is predicted to result in the amino acid substitution p.Ala606Thr. This variant was reported in the heterozygous state in numerous individuals with hemiplegic migraine and was found to co-segregate in at least four unrelated families (Riant et al. 2005. PubMed ID: 16088919; Jen et al. 2007. PubMed ID: 17435187; Podestà et al. 2011. PubMed ID: 21908445; Carreño et al. 2013. PubMed ID: 24498617; Hiekkala et al. 2018. PubMed ID: 29486580). Functional studies showed that this variant alters the sodium–potassium pump function (Tavraz et al. 2008. PubMed ID: 18728015). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-160100376-G-A). This variant is interpreted as pathogenic. |