Submissions for variant NM_000539.3(RHO):c.44A>G (p.Asn15Ser)

dbSNP: rs104893786

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001203907	SCV001375089	pathogenic	not provided	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 15 of the RHO protein (p.Asn15Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 8353500, 9483582). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13042). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt RHO protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects RHO function (PMID: 31100078). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000013917	SCV001443194	pathogenic	Retinitis pigmentosa 4	2020-09-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004814894	SCV005072360	likely pathogenic	Retinal dystrophy	2018-01-01	criteria provided, single submitter	clinical testing
SingHealth Duke-NUS Institute of Precision Medicine	RCV000013917	SCV005881660	pathogenic	Retinitis pigmentosa 4	2025-02-05	criteria provided, single submitter	clinical testing	Variant is located in a mutational hotspot where >50% of variants are pathogenic (PM1). Homozygous allele count in gnomAD exomes and genomse are less than 0, and variant is not found in genomes (PM2). Other variats at this amino acid residue have been classified as pathogenic (PM5, p.Asn15Lys; p.Asn15Ile). REVEL score is 0.788 (PP3_mod). + Experimental studies have shown that this missense change affects RHO function (PS3, PMID: 31100078)
OMIM	RCV000013917	SCV000034164	pathogenic	Retinitis pigmentosa 4	1993-11-01	no assertion criteria provided	literature only
Department of Ophthalmology and Visual Sciences Kyoto University	RCV000132598	SCV000172545	pathogenic	Retinitis pigmentosa		no assertion criteria provided	not provided	Converted during submission to Pathogenic.
Clinical Genetics, Academic Medical Center	RCV001203907	SCV001925349	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001203907	SCV001954106	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001203907	SCV001969414	pathogenic	not provided		no assertion criteria provided	clinical testing