ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3818C>T (p.Pro1273Leu) (rs758355520)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000169558 SCV000694455 pathogenic Wilson disease 2017-08-14 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.3818C>T (p.Pro1273Leu) variant located in the P-domain (Huster_2012)involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 4/120750 control chromosomes at a frequency of 0.0000331, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). Multiple publications have cited the variant in affected individuals. A clinical diagnostic laboratory classified this variant as "likely pathogenic." Taken together, this variant is classified as pathogenic.
Invitae RCV000169558 SCV000932274 pathogenic Wilson disease 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1273 of the ATP7B protein (p.Pro1273Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs758355520, ExAC 0.02%). This variant has been observed in the homozygous or compound heterozygous state in multiple individuals affected with Wilson disease and was observed to segregate with Wilson disease in at least one family (PMID: 20485189, 23551039, 15024742, 17272994). ClinVar contains an entry for this variant (Variation ID: 189139). This variant has been reported to affect ATP7B protein function (PMID: 22692182, 22240481). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000169558 SCV000221051 pathogenic Wilson disease 2018-10-18 no assertion criteria provided clinical testing

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