Submissions for variant NM_030665.4(RAI1):c.3692C>G (p.Pro1231Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003737578	SCV004553131	uncertain significance	not provided	2023-02-04	criteria provided, single submitter	clinical testing	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. 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 expected to disrupt RAI1 protein function. This variant has not been reported in the literature in individuals affected with RAI1-related conditions. This variant is present in population databases (rs763945694, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1231 of the RAI1 protein (p.Pro1231Arg).
PreventionGenetics, part of Exact Sciences	RCV004741708	SCV005365953	uncertain significance	RAI1-related disorder	2024-04-10	no assertion criteria provided	clinical testing	The RAI1 c.3692C>G variant is predicted to result in the amino acid substitution p.Pro1231Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.