Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002223070 | SCV002500736 | pathogenic | Bernard Soulier syndrome | 2022-03-29 | criteria provided, single submitter | clinical testing | Variant summary: GP1BA c.241T>C (p.Cys81Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249212 control chromosomes. c.241T>C has been reported in the literature in individuals affected with Bernard Soulier Syndrome including two siblings who were compound heterozygous for the variant (Kenny_1998) and a patient who was homozygous for the variant (Bragadottir_2014), suggesting an autosomal recessive inheritance pattern. However, Bragadottir_2014 also reported BSS carriers (including carriers of Cys81Arg), had significantly larger platelets and lower platelet counts than controls and some had mild thrombocytopenia. These data indicate that the variant is likely to be associated with disease. Experimental studies have shown that in transiently transfected cells stably expressing the GPb-IX complex, the expression of the variant was similar to the wild-type, but it did not bind vWF (Kenny_1998). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |