ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.910TTC[1] (p.Phe305del)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002648212 SCV003523466 likely pathogenic Familial hemiplegic migraine 2022-09-24 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been observed in individual(s) with familial hemiplegic migraine (PMID: 20837964). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This variant, c.913_915del, results in the deletion of 1 amino acid(s) of the ATP1A2 protein (p.Phe305del), but otherwise preserves the integrity of the reading frame.
Ambry Genetics RCV004072127 SCV004913940 likely pathogenic Inborn genetic diseases 2024-01-25 criteria provided, single submitter clinical testing The c.913_915delTTC (p.F305del) alteration, located in coding exon 8 of the ATP1A2 gene, results from an in-frame TTC deletion at nucleotide positions c.913 to c.915. This results in the deletion of a Phenylalanine residue at codon 305. Based on the available evidence, the ATP1A2 c.913_915delTTC (p.F305del) alteration is classified as likely pathogenic for autosomal dominant ATP1A2-related neurologic disorders; however, its clinical significance for autosomal recessive ATP1A2-related cortical malformation syndrome is uncertain. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was reported as a de novo occurrence in one individual with features of ATP1A2-related hemiplegic migraine, as well as detected in the heterozygous state in another individual and in two families with hemiplegic migraine (Riant, 2010; external communication). This amino acid position is highly conserved in available vertebrate species. Based on internal structural analysis, p.F305del is deleterious. This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as likely pathogenic.

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