Submissions for variant NM_018706.7(DHTKD1):c.487C>T (p.Arg163Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002785704	SCV003021540	pathogenic	2-aminoadipic 2-oxoadipic aciduria	2022-10-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. This variant is present in population databases (rs764591027, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg163*) in the DHTKD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DHTKD1 are known to be pathogenic (PMID: 23141293, 25860818).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002785704	SCV004122088	pathogenic	2-aminoadipic 2-oxoadipic aciduria	2023-10-24	criteria provided, single submitter	clinical testing	Variant summary: DHTKD1 c.487C>T (p.Arg163X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 1.2e-05 in 251486 control chromosomes (gnomAD). To our knowledge, no occurrence of c.487C>T in individuals affected with 2-Aminoadipic 2-Oxoadipic Aciduria and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.