Submissions for variant NM_000053.4(ATP7B):c.445G>A (p.Val149Met)

gnomAD frequency: 0.00016  dbSNP: rs200606656

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589823	SCV000694466	uncertain significance	not provided	2016-03-28	criteria provided, single submitter	clinical testing	Variant summary: This c.445G>A variant affects a conserved nucleotide, resulting in amino acid change from Val to Met. 4/5 in-silico tools predict this variant to be damaging. 5/5 programs in Alamut predict that this variant does not affect normal splicing. ESEFinder predicts that this variant may affect multiple ESE sites. However, this prediction has not been confirmed by experimental studies. This variant was found in 23/120652 control chromosomes from the broad and large populations of ExAC at a frequency of 0.0001906, which does not exceed the maximal expected frequency of a pathogenic allele (0.0054006) in this gene. To our knowledge, the variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical laboratories, nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant has currently been classified as a variant of uncertain significance (VUS) until additional information becomes available.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001111262	SCV001015377	likely benign	Wilson disease	2025-01-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001111262	SCV001268805	uncertain significance	Wilson disease	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001111262	SCV001977196	uncertain significance	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002530887	SCV003681509	uncertain significance	Inborn genetic diseases	2021-05-16	criteria provided, single submitter	clinical testing	The c.445G>A (p.V149M) alteration is located in exon 2 (coding exon 2) of the ATP7B gene. This alteration results from a G to A substitution at nucleotide position 445, causing the valine (V) at amino acid position 149 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV001111262	SCV003834485	uncertain significance	Wilson disease	2023-08-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000589823	SCV005396471	uncertain significance	not provided	2024-05-09	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc.	RCV001111262	SCV001460307	uncertain significance	Wilson disease	2020-04-15	no assertion criteria provided	clinical testing