Submissions for variant NM_173689.7(CRB2):c.3796G>C (p.Ala1266Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002720957	SCV003005869	uncertain significance	not provided	2022-03-11	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1266 of the CRB2 protein (p.Ala1266Pro). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CRB2-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 expected to disrupt CRB2 protein function. 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.
Ambry Genetics	RCV002720958	SCV003723147	uncertain significance	Inborn genetic diseases	2021-01-27	criteria provided, single submitter	clinical testing	The c.3796G>C (p.A1266P) alteration is located in exon 13 (coding exon 13) of the CRB2 gene. This alteration results from a G to C substitution at nucleotide position 3796, causing the alanine (A) at amino acid position 1266 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.