NM_000539.3(RHO):c.50C>T (p.Thr17Met) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 2, 2024
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:: RCV001090660.30

Allele description [Variation Report for NM_000539.3(RHO):c.50C>T (p.Thr17Met)]

NM_000539.3(RHO):c.50C>T (p.Thr17Met)

Gene:

RHO:rhodopsin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q22.1

Genomic location:

Preferred name:

NM_000539.3(RHO):c.50C>T (p.Thr17Met)

HGVS:

NC_000003.12:g.129528783C>T
NG_009115.1:g.5145C>T
NM_000539.3:c.50C>TMANE SELECT
NP_000530.1:p.Thr17Met
NC_000003.11:g.129247626C>T
P08100:p.Thr17Met

Protein change:

T17M; THR17MET

Links:

UniProtKB: P08100#VAR_004767; OMIM: 180380.0006; dbSNP: rs104893769

NCBI 1000 Genomes Browser:

rs104893769

Molecular consequence:

NM_000539.3:c.50C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001246333	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jun 1, 2022)	germline	clinical testing	Citation Link,
SCV001480138	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001583958	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 2, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 1897520, 28559085, 19913029, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001246333

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jun 1, 2022)

germline

clinical testing

Citation Link,

SCV001480138

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001583958

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 2, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis.

Sheffield VC, Fishman GA, Beck JS, Kimura AE, Stone EM.

Am J Hum Genet. 1991 Oct;49(4):699-706.

PubMed [citation]

PMID:: 1897520
PMCID:: PMC1683182

See all PubMed Citations (5)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001246333.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

RHO: PP1:Strong, PM2, PS3:Moderate, PS4:Moderate

#	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		3	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001480138.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001583958.4

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

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 17 of the RHO protein (p.Thr17Met). This variant is present in population databases (rs104893769, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal dominant retinitis pigmentosa (PMID: 1897520, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13018). 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: 19913029). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Nov 30, 2024

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