ClinVar

Description

A variant of uncertain significance has been identified in the RASA1 gene. Although the P868L variant has not been published as pathogenic or been reported as benign to our knowledge, it has been classified as a variant of uncertain significance by another clinical laboratory in ClinVar (SCV000552994.1; Landrum et al., 2016). This variant is observed in 15/125,660 alleles (0.012%) from individuals of European (Non-Finnish) ancestry in large population cohorts (Lek et al., 2016). This nucleotide substitution (c.2603 C>T) occurs at the last nucleotide of exon 19, a position at which nucleotide substitutions commonly result in abnormal gene splicing (Buratti et al., 2007). Nevertheless, several in silico splice predictions models predict that the c.2603 C>T substitution does not cause abnormal gene splicing. Additionally, although the P868L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.