ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.1666A>T (p.Asn556Tyr) (rs141467566)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724781 SCV000225804 uncertain significance not provided 2015-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000186772 SCV000240340 likely benign not specified 2013-01-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000400047 SCV000349900 uncertain significance Alternating hemiplegia of childhood 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000296463 SCV000349901 uncertain significance Familial hemiplegic migraine 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000296463 SCV000824605 uncertain significance Familial hemiplegic migraine 2018-11-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine with tyrosine at codon 556 of the ATP1A2 protein (p.Asn556Tyr). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and tyrosine. This variant is present in population databases (rs141467566, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with ATP1A2-related disease. ClinVar contains an entry for this variant (Variation ID: 194183). 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 C65"). 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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