Submissions for variant NM_020812.4(DOCK6):c.3163G>A (p.Val1055Met)

dbSNP: rs202209921

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001978238	SCV002271118	uncertain significance	not provided	2022-10-19	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1055 of the DOCK6 protein (p.Val1055Met). This variant is present in population databases (rs202209921, gnomAD 0.3%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with congenital heart disease (PMID: 30293987). ClinVar contains an entry for this variant (Variation ID: 1489179). 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 expected to disrupt DOCK6 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.
Ambry Genetics	RCV002592597	SCV003677011	likely benign	Inborn genetic diseases	2022-01-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
CeGaT Center for Human Genetics Tuebingen	RCV001978238	SCV004137833	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003923402	SCV004741590	likely benign	DOCK6-related disorder	2022-04-20	criteria provided, single submitter	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).