Submissions for variant NM_002890.3(RASA1):c.1171C>T (p.Arg391Trp)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Genomics Laboratory, Washington University in St. Louis	RCV005052287	SCV005685446	uncertain significance	Capillary malformation-arteriovenous malformation 1	2024-12-09	criteria provided, single submitter	clinical testing	A RASA1 c.1171C>T (p.Arg391Trp) variant was identified at a near heterozygous allelic fraction of 47.9%, a frequency which may be consistent with germline origin. This variant, to our knowledge, has not been reported in the medical literature. It is only observed on 3/1,611,826 alleles in the general population (gnomAD v.4.1.0), indicating it is not a common variant. Computational predictors indicate that the variant is damaging, evidence that correlates with impact to RASA1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005105384	SCV005827158	uncertain significance	Capillary malformation-arteriovenous malformation syndrome	2024-08-20	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 391 of the RASA1 protein (p.Arg391Trp). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with RASA1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.