ClinVar Miner

Submissions for variant NM_000052.7(ATP7A):c.1384C>G (p.Pro462Ala) (rs781964005)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493697 SCV000582352 uncertain significance not specified 2017-05-04 criteria provided, single submitter clinical testing The P462A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P462A variant is observed in 1/10095 (0.01%) alleles as a hemizygous variant from an individual of South Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function.
Invitae RCV001241257 SCV001414263 uncertain significance Menkes kinky-hair syndrome; Cutis laxa, X-linked; Distal spinal muscular atrophy, X-linked 3 2019-06-10 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 462 of the ATP7A protein (p.Pro462Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs781964005, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATP7A-related disease. ClinVar contains an entry for this variant (Variation ID: 429718). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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