Submissions for variant NM_006009.4(TUBA1A):c.53A>G (p.Asn18Ser)

dbSNP: rs1064795213

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482824	SCV000570818	pathogenic	not provided	2023-02-02	criteria provided, single submitter	clinical testing	Identified in presumably affected individuals in the published literature, but familial segregation information and clinical information were not included (Hebebrand et al., 2019; Meng et al., 2017); 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: 30744660, 28973083)
Genetic Services Laboratory, University of Chicago	RCV000501252	SCV000597719	uncertain significance	not specified	2015-09-18	criteria provided, single submitter	clinical testing
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000767453	SCV000898068	likely pathogenic	Tubulinopathy	2018-07-01	criteria provided, single submitter	literature only	A variant that is classified as likely pathogenic has been identified in the TUBA1A gene in a born individual of unknown sex. The c.53A>G, p.(Asn18Ser) variant has been reported as a variant of germline/unknown origin.
Genomic Medicine Lab, University of California San Francisco	RCV001376064	SCV001573087	pathogenic	Lissencephaly due to TUBA1A mutation	2021-02-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000482824	SCV003441129	uncertain significance	not provided	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 18 of the TUBA1A protein (p.Asn18Ser). This variant is not present in population databases (gnomAD no frequency). 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. This variant disrupts the p.Asn18 amino acid residue in TUBA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 TUBA1A protein function. ClinVar contains an entry for this variant (Variation ID: 421567). This missense change has been observed in individual(s) with TUBA1A-related conditions (PMID: 28973083).