Submissions for variant NM_030773.4(TUBB1):c.637C>T (p.Arg213Cys)

gnomAD frequency: 0.00002  dbSNP: rs777100651

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003093965	SCV003328571	uncertain significance	not provided	2022-11-14	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs777100651, gnomAD 0.006%). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TUBB1 protein function. ClinVar contains an entry for this variant (Variation ID: 1684425). This variant has not been reported in the literature in individuals affected with TUBB1-related conditions. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 213 of the TUBB1 protein (p.Arg213Cys).
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245431	SCV002515680	uncertain significance	Macrothrombocytopenia, isolated, 1, autosomal dominant		no assertion criteria provided	research