ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1924G>C (p.Asp642His) (rs72552285)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169521 SCV000220995 likely pathogenic Wilson disease 2014-12-29 criteria provided, single submitter literature only
Invitae RCV000169521 SCV000626833 likely pathogenic Wilson disease 2017-07-27 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 642 of the ATP7B protein (p.Asp642His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous in three individuals affected with Wilson disease (PMID: 24706876, 21610751, 21682854) and in an individual with a copper metabolism disorder (Invitae). It was also reported in individuals affected with Wilson disease where the second allele was not reported (PMID: 18483695, 22308153). ClinVar contains an entry for this variant (Variation ID: 189109). Experimental studies have shown that this missense change can restore growth rate and copper transport activity to yeast cells lacking the yeast homolog of ATP7B in a similar manner to the wild type protein (PMID: 18203200). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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