Submissions for variant NM_000052.7(ATP7A):c.1856T>C (p.Ile619Thr)

dbSNP: rs1569549841

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002318099	SCV000849782	likely benign	Inborn genetic diseases	2017-10-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics	RCV000990879	SCV001141931	likely benign	Menkes kinky-hair syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV001862055	SCV002221759	uncertain significance	Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3	2022-09-19	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 619 of the ATP7A protein (p.Ile619Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATP7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 589159). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATP7A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV003908003	SCV004722257	uncertain significance	ATP7A-related condition	2023-11-10	criteria provided, single submitter	clinical testing	The ATP7A c.1856T>C variant is predicted to result in the amino acid substitution p.Ile619Thr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.