Submissions for variant NM_018706.7(DHTKD1):c.970A>G (p.Arg324Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003370078	SCV004082863	uncertain significance	Inborn genetic diseases	2023-08-08	criteria provided, single submitter	clinical testing	The c.970A>G (p.R324G) alteration is located in exon 5 (coding exon 5) of the DHTKD1 gene. This alteration results from a A to G substitution at nucleotide position 970, causing the arginine (R) at amino acid position 324 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003778062	SCV004637097	uncertain significance	2-aminoadipic 2-oxoadipic aciduria	2023-02-14	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs549007510, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 324 of the DHTKD1 protein (p.Arg324Gly). This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. 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 DHTKD1 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.