Submissions for variant NM_030665.4(RAI1):c.1970C>T (p.Ala657Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002616444	SCV003509371	uncertain significance	not provided	2024-06-15	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 657 of the RAI1 protein (p.Ala657Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2190540). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RAI1 protein function with a negative predictive value of 80%. 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.
PreventionGenetics, part of Exact Sciences	RCV003936606	SCV004753525	uncertain significance	RAI1-related disorder	2024-09-13	no assertion criteria provided	clinical testing	The RAI1 c.1970C>T variant is predicted to result in the amino acid substitution p.Ala657Val. To our knowledge, this variant has not been reported in the literature. This variant was not observed in the gnomAD v2.1.1 population database, but is present in 35 alleles in gnomADv4.0.0. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.