ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.2374A>G (p.Ile792Val) (rs758749177)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186799 SCV000240368 uncertain significance not provided 2018-09-04 criteria provided, single submitter clinical testing p.Ile792Val (ATT>GTT): c.2374 A>G in exon 17 of the ATP1A2 gene (NM_000702.3). The I792V missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I792V variant alters a conserved position in the ATP1A2 protein. However, the amino acid substitution is conservative, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether I792V is a disease-causing mutation or a rare benign variant. The variant is found in ADULT-EPI,EPILEPSY panel(s).
Invitae RCV000635220 SCV000756603 uncertain significance Familial hemiplegic migraine 2018-11-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 792 of the ATP1A2 protein (p.Ile792Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs758749177, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATP1A2-related disease. ClinVar contains an entry for this variant (Variation ID: 204897). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.

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