Submissions for variant NM_006009.4(TUBA1A):c.1168C>T (p.Arg390Cys)

dbSNP: rs1064793286

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483973	SCV000565643	pathogenic	not provided	2023-06-18	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; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 24860126, 33604570, 30744660, 29057214, 28252636, 22948023, 20466733, 34426522)
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000767411	SCV000898026	pathogenic	Tubulinopathy	2018-07-01	criteria provided, single submitter	literature only	A variant that is classified as pathogenic has been identified in the TUBA1A gene in a born individual of unknown sex. The c.1168C>T, p.(Arg390Cys) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Kumar et al. Hum Mol Genet, 2010 PMID: 20466733. HPO-standardized clinical features were: Agenesis of the corpus callosum (HP:0001274); Cortical gyral simplification (HP:0009879); Cerebellar hypoplasia (HP:0001321)
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV001805098	SCV002053759	likely pathogenic	Lissencephaly due to TUBA1A mutation		criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001805098	SCV004027715	pathogenic	Lissencephaly due to TUBA1A mutation	2023-07-25	criteria provided, single submitter	clinical testing	Criteria applied: PS4,PM5_STR,PM1,PM2_SUP,PP3
Labcorp Genetics (formerly Invitae), Labcorp	RCV000483973	SCV005836020	pathogenic	not provided	2024-12-10	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 390 of the TUBA1A protein (p.Arg390Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cortical malformation(s) (PMID: 20466733, 22948023). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 418531). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TUBA1A protein function with a positive predictive value of 80%. This variant disrupts the p.Arg390 amino acid residue in TUBA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23317684, 28677066). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Service de Génétique Moléculaire, Hôpital Robert Debré	RCV001257007	SCV001433563	likely pathogenic	Rare genetic intellectual disability		no assertion criteria provided	clinical testing