Submissions for variant NM_018706.7(DHTKD1):c.748del (p.Glu250fs)

dbSNP: rs1564391327

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000691193	SCV000818940	pathogenic	2-aminoadipic 2-oxoadipic aciduria	2018-03-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu250Asnfs*16) in the DHTKD1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DHTKD1-related disease. Loss-of-function variants in DHTKD1 are known to be pathogenic (PMID: 23141293, 25860818). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000691193	SCV005077692	pathogenic	2-aminoadipic 2-oxoadipic aciduria	2024-04-17	criteria provided, single submitter	clinical testing	Variant summary: DHTKD1 c.748delG (p.Glu250AsnfsX16) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251252 control chromosomes. To our knowledge, no occurrence of c.748delG in individuals affected with 2-Aminoadipic 2-Oxoadipic Aciduria and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 570348). Based on the evidence outlined above, the variant was classified as pathogenic.