ClinVar Miner

Submissions for variant NM_018706.7(DHTKD1):c.1118C>T (p.Pro373Leu)

gnomAD frequency: 0.00001  dbSNP: rs556384043
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001250095 SCV004685806 uncertain significance 2-aminoadipic 2-oxoadipic aciduria 2023-08-25 criteria provided, single submitter clinical testing 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. 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. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 373 of the DHTKD1 protein (p.Pro373Leu). This variant is present in population databases (rs556384043, gnomAD 0.005%). 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: 973472).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003989657 SCV004807281 uncertain significance Charcot-Marie-Tooth disease axonal type 2Q 2024-03-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003994245 SCV004813167 uncertain significance not specified 2024-02-20 criteria provided, single submitter clinical testing Variant summary: DHTKD1 c.1118C>T (p.Pro373Leu) results in a non-conservative amino acid change located in the Dehydrogenase, E1 component (IPR001017) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251404 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1118C>T 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: 973472). Based on the evidence outlined above, the variant was classified as uncertain significance.
Elsea Laboratory, Baylor College of Medicine RCV001250095 SCV001424282 likely pathogenic 2-aminoadipic 2-oxoadipic aciduria 2020-04-01 no assertion criteria provided clinical testing

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