ClinVar Miner

Submissions for variant NM_000052.7(ATP7A):c.2531G>A (p.Arg844His) (rs367775730)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235797 SCV000292488 uncertain significance not specified 2017-09-12 criteria provided, single submitter clinical testing The R844H variant in the ATP7A gene has been previously reported in patients with either moderate or classic forms of Menkes disease (Moller et al. 2005). The Arg844 residue lies in one of three cytoplasmic domains, the (A) activation domain, a highly conserved region across copper P-type ATPases. Immunoflourescence studies using fibroblasts with the R844H mutation revealed no ATP7A signal, indicating either failure to synthesize protein or its very rapid degradation (Moller et al. 2005). The R844H variant was observed at a very low level in 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project; however, this variant was reported in one male individual. The R844H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species; however, Histidine is observed at this position in one other mammalian species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001085537 SCV000639975 benign Menkes kinky-hair syndrome; Cutis laxa, X-linked; Distal spinal muscular atrophy, X-linked 3 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000529093 SCV001150389 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing

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