Submissions for variant NM_000539.3(RHO):c.491C>T (p.Ala164Val)

gnomAD frequency: 0.00002  dbSNP: rs104893793

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001229601	SCV001402052	pathogenic	not provided	2024-01-12	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 164 of the RHO protein (p.Ala164Val). This variant is present in population databases (rs104893793, gnomAD 0.003%). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 7981701, 11139241, 17488458). ClinVar contains an entry for this variant (Variation ID: 417867). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RHO protein function. Experimental studies have shown that this missense change affects RHO function (PMID: 9380676, 19913029, 30240733). This variant disrupts the p.Ala164 amino acid residue in RHO. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8088850, 29847639). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV001265187	SCV001443219	likely pathogenic	Retinitis pigmentosa 4	2020-09-01	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003889904	SCV004705657	likely pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477900	SCV000536724	pathogenic	Congenital stationary night blindness autosomal dominant 1	2015-09-30	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787680	SCV000926671	pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787681	SCV000926672	pathogenic	Cone-rod dystrophy	2018-04-01	no assertion criteria provided	research