Submissions for variant NM_006343.3(MERTK):c.2180G>A (p.Arg727Gln)

dbSNP: rs878853354

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001383851	SCV001583160	pathogenic	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This missense change has been observed in individuals with clinical features of autosomal recessive retinitis pigmentosa (PMID: 24625443, 28041643, 29659094; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 727 of the MERTK protein (p.Arg727Gln). ClinVar contains an entry for this variant (Variation ID: 236454). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg727 amino acid residue in MERTK. Other variant(s) that disrupt this residue have been observed in individuals with MERTK-related conditions (PMID: 28041643), which suggests that this may be a clinically significant amino acid residue. 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 MERTK protein function.
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000225669	SCV000282560	uncertain significance	Retinal dystrophy		no assertion criteria provided	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505072	SCV000598748	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research