ClinVar Miner

Submissions for variant NM_004320.6(ATP2A1):c.1442A>T (p.Lys481Met)

gnomAD frequency: 0.00001  dbSNP: rs1288758939
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039083 SCV001202594 uncertain significance Brody myopathy 2021-12-27 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 481 of the ATP2A1 protein (p.Lys481Met). This variant has not been reported in the literature in individuals affected with ATP2A1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 837692).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265932 SCV002547720 uncertain significance not specified 2022-05-02 criteria provided, single submitter clinical testing Variant summary: ATP2A1 c.1442A>T (p.Lys481Met) results in a non-conservative amino acid change located in the P-type ATPase, haloacid dehalogenase domain (IPR044492) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251476 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1442A>T in individuals affected with Brody Myopathy and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002553051 SCV003672889 uncertain significance Inborn genetic diseases 2022-12-19 criteria provided, single submitter clinical testing The c.1442A>T (p.K481M) alteration is located in exon 13 (coding exon 13) of the ATP2A1 gene. This alteration results from a A to T substitution at nucleotide position 1442, causing the lysine (K) at amino acid position 481 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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