Submissions for variant NM_000053.4(ATP7B):c.4106C>T (p.Ser1369Leu)

dbSNP: rs1555282678

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000672293	SCV000797389	uncertain significance	Wilson disease	2018-01-30	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000672293	SCV004210671	pathogenic	Wilson disease	2022-07-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689846	SCV005185139	uncertain significance	not specified	2024-05-31	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.4106C>T (p.Ser1369Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246918 control chromosomes. c.4106C>T has been reported in the literature in the homozygous, compound heterozygous, or unknown state (2nd allele not specified) in individuals affected with Wilson Disease (example, Lepori_2007, Li_2013, Nicastro_2010, Zarina_2017). These data indicate that the variant may be associated with 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: 17949296, 23235335, 20967755, 24661374, 31942415, 28717664). ClinVar contains an entry for this variant (Variation ID: 556300). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.