ClinVar

Description

Experimental studies have shown that this missense change affects GP1BA function (PMID: 1694864, 7690774, 11222377, 19067792). For these reasons, this variant has been classified as Pathogenic. 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 GP1BA protein function. ClinVar contains an entry for this variant (Variation ID: 4156). This variant is also known as Bolzano mutation, Ala156Val. This missense change has been observed in individuals with the classical form of autosomal recessive Bernard-Soulier syndrome. It has also been reported in a heterozygous state with autosomal dominant macrothrombocytopenia in many families and has been considered as the most frequent cause of inherited thrombocytopenia in Italy (PMID: 7690774, 10235425, 11222377, 19067792, 21933849). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 172 of the GP1BA protein (p.Ala172Val).