Submissions for variant NM_006087.4(TUBB4A):c.286G>A (p.Gly96Arg)

dbSNP: rs1131691696

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493968	SCV000582648	pathogenic	not provided	2021-08-03	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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: 33144682, 24785942, 31692161, 28592043, 28791129)
CeGaT Center for Human Genetics Tuebingen	RCV000493968	SCV000780610	likely pathogenic	not provided	2018-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851359	SCV002204903	pathogenic	Hypomyelinating leukodystrophy 6	2024-01-06	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 96 of the TUBB4A protein (p.Gly96Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TUBB4A-related conditions (PMID: 28592043, 28791129, 31692161; Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as c.70G>A and c.439G>A. ClinVar contains an entry for this variant (Variation ID: 429952). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001851359	SCV005091968	likely pathogenic	Hypomyelinating leukodystrophy 6	2024-08-02	criteria provided, single submitter	clinical testing
GenomeConnect - Brain Gene Registry	RCV003458202	SCV004176868	not provided	Torsion dystonia 4; Hypomyelinating leukodystrophy 6		no assertion provided	phenotyping only	Variant classified as Pathogenic and reported on 02-20-2020 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.