Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001092106 | SCV001248470 | pathogenic | not provided | 2019-09-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV001092106 | SCV001448117 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000258636 | SCV001502990 | pathogenic | Hypomyelinating leukodystrophy 6 | 2023-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 391 of the TUBB4A protein (p.Arg391His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hypomyelinating leukodystrophy (PMID: 25085639; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 267793). 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 TUBB4A protein function. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001092106 | SCV003924637 | pathogenic | not provided | 2023-05-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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: 27809427, 26934450, 27159321, 35661708, 32681585, 36463079, 34997144, 34788679, 33547136, 34514881, 25085639, 35599849) |
Gene |
RCV000258636 | SCV000328481 | not provided | Hypomyelinating leukodystrophy 6 | no assertion provided | literature only | ||
Genome |
RCV001249222 | SCV001423156 | not provided | Torsion dystonia 4; Hypomyelinating leukodystrophy 6 | no assertion provided | phenotyping only | Variant interpretted as Pathogenic and reported on 03-12-2018 by Lab or GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |