ClinVar Miner

Submissions for variant NM_000052.7(ATP7A):c.4102G>A (p.Val1368Ile)

dbSNP: rs782483019
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236031 SCV000292953 uncertain significance not provided 2015-07-18 criteria provided, single submitter clinical testing The V1368I variant in the ATP7A gene has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. The V1368I variant 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 V1368I variant is a conservative amino acid substitution that occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (A1362D, A1362V, G1369R, A1373P, A1373V) have been reported in the Human Gene Mutation Database in association with Menkes syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret V1368I as a variant of unknown significance
Invitae RCV001274026 SCV003507524 uncertain significance Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 2022-11-08 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP7A protein function. ClinVar contains an entry for this variant (Variation ID: 245812). This variant has not been reported in the literature in individuals affected with ATP7A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1368 of the ATP7A protein (p.Val1368Ile).
Natera, Inc. RCV001274026 SCV001457716 uncertain significance Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 2020-09-16 no assertion criteria provided clinical testing

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