Submissions for variant NM_000053.4(ATP7B):c.3209C>G (p.Pro1070Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003328934	SCV004035605	likely pathogenic	not provided	2023-08-11	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27022412, 30556376)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526983	SCV005040282	uncertain significance	not specified	2024-03-14	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.3209C>G (p.Pro1070Arg) results in a non-conservative amino acid change located in the heavy metal translocating P-type ATPase domain (IPR027256) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249398 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3209C>G has been reported in the literature in multiple individuals affected with Wilson Disease with unspecified genotypes (e.g. Dong_2016, Li_2021, Zhang_2016). These reports do not provide unequivocal conclusions about association of the variant with Wilson Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27022412, 34470610, 30556376, 27706781). ClinVar contains an entry for this variant (Variation ID: 2579959). Based on the evidence outlined above, the variant was classified as uncertain significance.