ClinVar Miner

Submissions for variant NM_018706.7(DHTKD1):c.1408G>A (p.Gly470Arg)

gnomAD frequency: 0.00005  dbSNP: rs35898320
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757152 SCV000885280 uncertain significance not provided 2018-01-18 criteria provided, single submitter clinical testing The p.Gly470Arg variant (rs35898320) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.01 percent in the African population (identified on 3 out of 24,030 chromosomes). The glycine at position 470 is highly conserved up to baker’s yeast considering 11 species (Alamut v2.10) and computational analyses of the p.Gly470Arg variant on protein structure and function indicate a deleterious effect (SIFT: deleterious, MutationTaster: disease causing, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Gly470Arg variant with certainty.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855889 SCV002120395 uncertain significance 2-aminoadipic 2-oxoadipic aciduria 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 470 of the DHTKD1 protein (p.Gly470Arg). This variant is present in population databases (rs35898320, gnomAD 0.01%). 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: 618591). 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%. 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 RCV002536565 SCV003680545 uncertain significance Inborn genetic diseases 2022-12-28 criteria provided, single submitter clinical testing The c.1408G>A (p.G470R) alteration is located in exon 8 (coding exon 8) of the DHTKD1 gene. This alteration results from a G to A substitution at nucleotide position 1408, causing the glycine (G) at amino acid position 470 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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