ClinVar Miner

Submissions for variant NM_000052.7(ATP7A):c.1802C>A (p.Thr601Asn) (rs371777895)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000443197 SCV000530858 uncertain significance not specified 2016-08-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ATP7A gene. The T601N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T601N variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the T601N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001035427 SCV001198754 uncertain significance Menkes kinky-hair syndrome; Cutis laxa, X-linked; Distal spinal muscular atrophy, X-linked 3 2019-04-02 criteria provided, single submitter clinical testing This sequence change replaces threonine with asparagine at codon 601 of the ATP7A protein (p.Thr601Asn). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs371777895, ExAC 0.002%). This variant has not been reported in the literature in individuals with ATP7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 388532). 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"). 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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