Submissions for variant NM_030665.4(RAI1):c.1229A>C (p.Gln410Pro)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003578587	SCV004333521	uncertain significance	not provided	2024-05-14	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 410 of the RAI1 protein (p.Gln410Pro). This variant is present in population databases (rs199885507, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with RAI1-related conditions. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003578587	SCV005436373	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	RAI1: BP4
PreventionGenetics, part of Exact Sciences	RCV004741648	SCV005348913	uncertain significance	RAI1-related disorder	2024-09-24	no assertion criteria provided	clinical testing	The RAI1 c.1229A>C variant is predicted to result in the amino acid substitution p.Gln410Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.