Submissions for variant NM_058246.4(DNAJB6):c.974A>C (p.Asn325Thr)

gnomAD frequency: 0.00008  dbSNP: rs375911119

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000730064	SCV000857774	uncertain significance	not provided	2017-11-02	criteria provided, single submitter	clinical testing
Invitae	RCV000794806	SCV000934237	uncertain significance	Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	2023-12-09	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 325 of the DNAJB6 protein (p.Asn325Thr). This variant is present in population databases (rs375911119, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DNAJB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 594710). 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 DNAJB6 protein function with a positive predictive value of 80%. 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.
GeneDx	RCV000730064	SCV000968551	likely benign	not provided	2018-05-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Revvity Omics, Revvity	RCV000794806	SCV003831779	uncertain significance	Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	2022-11-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003353009	SCV004056247	uncertain significance	Inborn genetic diseases	2023-08-04	criteria provided, single submitter	clinical testing	The c.974A>C (p.N325T) alteration is located in exon 10 (coding exon 9) of the DNAJB6 gene. This alteration results from a A to C substitution at nucleotide position 974, causing the asparagine (N) at amino acid position 325 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000794806	SCV004562165	uncertain significance	Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	2023-10-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000730064	SCV004699909	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	DNAJB6: BP4