NM_000539.3(RHO):c.173C>G (p.Thr58Arg) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 24, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001384460.7

Allele description [Variation Report for NM_000539.3(RHO):c.173C>G (p.Thr58Arg)]

NM_000539.3(RHO):c.173C>G (p.Thr58Arg)

Gene:

RHO:rhodopsin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q22.1

Genomic location:

Preferred name:

NM_000539.3(RHO):c.173C>G (p.Thr58Arg)

HGVS:

NC_000003.12:g.129528906C>G
NG_009115.1:g.5268C>G
NM_000539.3:c.173C>GMANE SELECT
NP_000530.1:p.Thr58Arg
NC_000003.11:g.129247749C>G
P08100:p.Thr58Arg

Protein change:

T58R; THR58ARG

Links:

UniProtKB: P08100#VAR_004779; OMIM: 180380.0004; dbSNP: rs28933394

NCBI 1000 Genomes Browser:

rs28933394

Molecular consequence:

NM_000539.3:c.173C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001583961	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 27, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 1924344, 2215617, 29847639, 28492532
SCV004030981	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Aug 24, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001583961

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 27, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004030981

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Aug 24, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa.

Sung CH, Schneider BG, Agarwal N, Papermaster DS, Nathans J.

Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8840-4.

PubMed [citation]

PMID:: 1924344
PMCID:: PMC52606

Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa.

Dryja TP, McGee TL, Hahn LB, Cowley GS, Olsson JE, Reichel E, Sandberg MA, Berson EL.

N Engl J Med. 1990 Nov 8;323(19):1302-7.

PubMed [citation]

PMID:: 2215617

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001583961.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RHO function (PMID: 1924344). 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 RHO protein function. ClinVar contains an entry for this variant (Variation ID: 13016). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 2215617, 29847639). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 58 of the RHO protein (p.Thr58Arg).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV004030981.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 2333895, 15823756, 21094163, 8486634, 1924344, 2215617, 36648560, 30977563, 32483926, 25408095, 32882181, 32795431, 31717845, 29847639, 33777460, 31908405, 1929926, 28981474, 32037395, 18385078, 1882937, 8328469)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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