Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000624586 | SCV000741616 | pathogenic | Inborn genetic diseases | 2016-06-20 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000149817 | SCV000893333 | pathogenic | Catel-Manzke syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001092080 | SCV001248438 | pathogenic | not provided | 2018-02-01 | criteria provided, single submitter | clinical testing | |
Hudson |
RCV000149817 | SCV001439371 | pathogenic | Catel-Manzke syndrome | 2020-08-26 | criteria provided, single submitter | research | ACMG codes:PS4, PM2, PM3, PP3, PP5 |
Gene |
RCV001092080 | SCV001795815 | pathogenic | not provided | 2023-08-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28422407, 26366375, 25480037, 24326962, 21834032, 18501694, 14564220, 34426522, 31769200, 31833187, 34012376, 34930662, 29431110, 27535533) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000149817 | SCV002572361 | pathogenic | Catel-Manzke syndrome | 2022-08-26 | criteria provided, single submitter | clinical testing | Variant summary: TGDS c.298G>T (p.Ala100Ser) results in a conservative amino acid change located in the NAD(P)-binding domain (IPR016040) 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 0.00033 in 206418 control chromosomes. This frequency does not allow conclusions about variant significance. c.298G>T has been reported in the literature as a biallelic genotype in multiple individuals affected with Catel-Manzke Syndrome (example, Ehmke_2014, Miller_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001092080 | SCV003258522 | pathogenic | not provided | 2022-09-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 100 of the TGDS protein (p.Ala100Ser). This variant is present in population databases (rs140430952, gnomAD 0.06%). This missense change has been observed in individuals with atypical or typical Catel-Manzke syndrome (PMID: 25480037, 26366375, 28422407, 31769200). ClinVar contains an entry for this variant (Variation ID: 162455). 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 expected to disrupt TGDS protein function. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000149817 | SCV003811576 | likely pathogenic | Catel-Manzke syndrome | 2021-12-22 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV003415988 | SCV004118257 | pathogenic | TGDS-related condition | 2023-08-03 | criteria provided, single submitter | clinical testing | The TGDS c.298G>T variant is predicted to result in the amino acid substitution p.Ala100Ser. This variant has been reported as a most common pathogenic variant for Catel-Manzke Syndrome (Ehmke. 2014. PubMed ID: 25480037; Pferdehirt et al. 2015. PubMed ID: 26366375; Schoner et al. 2017. PubMed ID: 28422407). This variant is reported in 0.063% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-95243122-C-A). This variant is interpreted as pathogenic. |
OMIM | RCV000149817 | SCV000196644 | pathogenic | Catel-Manzke syndrome | 2014-12-04 | no assertion criteria provided | literature only | |
Equipe Genetique des Anomalies du Developpement, |
RCV000149817 | SCV001439349 | pathogenic | Catel-Manzke syndrome | 2020-09-25 | no assertion criteria provided | clinical testing |