Submissions for variant NM_018706.7(DHTKD1):c.2662C>A (p.Arg888Ser)

dbSNP: rs143212640

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001064904	SCV001229840	uncertain significance	2-aminoadipic 2-oxoadipic aciduria	2023-11-18	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 888 of the DHTKD1 protein (p.Arg888Ser). This variant is present in population databases (rs143212640, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 858915). 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 with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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	RCV002274131	SCV002559292	uncertain significance	not provided	2022-02-04	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV004030563	SCV004857004	uncertain significance	Inborn genetic diseases	2024-02-02	criteria provided, single submitter	clinical testing	The c.2662C>A (p.R888S) alteration is located in exon 17 (coding exon 17) of the DHTKD1 gene. This alteration results from a C to A substitution at nucleotide position 2662, causing the arginine (R) at amino acid position 888 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics	RCV002274131	SCV005190637	uncertain significance	not provided		criteria provided, single submitter	not provided
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV002274131	SCV005197711	uncertain significance	not provided	2022-11-07	criteria provided, single submitter	clinical testing