Submissions for variant NM_000053.4(ATP7B):c.1198A>G (p.Thr400Ala)

gnomAD frequency: 0.00066  dbSNP: rs199807461

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000804503	SCV000944415	likely benign	Wilson disease	2025-01-28	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001508351	SCV001714461	uncertain significance	not provided	2019-12-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000804503	SCV001977186	uncertain significance	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001508351	SCV002547244	uncertain significance	not provided	2022-07-05	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 reported as pathogenic or benign in association with neurodevelopmental disorders to our knowledge; This variant is associated with the following publications: (PMID: 35637795)
All of Us Research Program, National Institutes of Health	RCV000804503	SCV004815232	uncertain significance	Wilson disease	2024-09-23	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with alanine at codon 400 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has been identified in 52/280962 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc.	RCV000804503	SCV001463853	uncertain significance	Wilson disease	2020-09-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003928277	SCV004742609	likely benign	ATP7B-related disorder	2022-09-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).