Submissions for variant NM_006009.4(TUBA1A):c.652G>A (p.Asp218Asn)

dbSNP: rs1057517858

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414596	SCV000490901	pathogenic	not provided	2021-12-14	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); 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: 31628766, 33077954, 31474318)
Ambry Genetics	RCV000623405	SCV000742902	pathogenic	Inborn genetic diseases	2019-09-19	criteria provided, single submitter	clinical testing
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000767505	SCV000898120	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.652G>A, p.(Asp218Asn) variant has been reported as a variant of germline/unknown origin.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262357	SCV001440188	likely pathogenic	Lissencephaly due to TUBA1A mutation	2019-01-01	criteria provided, single submitter	clinical testing
Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg	RCV001803691	SCV002047681	likely pathogenic	Tubulinopathy-associated dysgyria	2021-11-01	criteria provided, single submitter	research
Invitae	RCV000414596	SCV002166420	uncertain significance	not provided	2022-03-30	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 372561). This missense change has been observed in individual(s) with TUBA1A-related conditions (PMID: 31474318, 31628766, 33077954). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 218 of the TUBA1A protein (p.Asp218Asn).
Dobyns Lab, Seattle Children's Research Institute	RCV000779653	SCV000916332	pathogenic	Lissencephaly due to TUBA1A mutation; Corpus callosum, agenesis of; Genetic syndrome with a Dandy-Walker malformation as major feature	2019-02-18	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001258014	SCV001434828	likely pathogenic	Dandy-Walker syndrome		no assertion criteria provided	research