Submissions for variant NM_000053.4(ATP7B):c.509G>T (p.Gly170Val)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004703086	SCV005202835	uncertain significance	not specified	2024-07-24	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.509G>T (p.Gly170Val) results in a non-conservative amino acid change located in the Heavy metal-associated domain, HMA (IPR006121) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.509G>T has been reported in the literature in at least one individual affected with Wilson Disease without reported genotype (e.g. Lepori_2012). This report does 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 publication has been ascertained in the context of this evaluation (PMID: 22484412). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance.