VCV000010505.1 - ClinVar

NM_020061.6(OPN1LW):c.607T>C (p.Cys203Arg)

Interpretation:: Pathogenic
Review status:: criteria provided, single submitter
Submissions:: 2 (Most recent: Jul 13, 2017)
Last evaluated:: Jul 2, 2015
Accession:: VCV000010505.1
Variation ID:: 10505
Description:: single nucleotide variant

NM_020061.6(OPN1LW):c.607T>C (p.Cys203Arg)

Allele ID

25544

Variant type

single nucleotide variant

Variant length

1 bp

Cytogenetic location

Xq28

Genomic location

X: 154154602 (GRCh38) GRCh38 UCSC

X: 153420077 (GRCh37) GRCh37 UCSC

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.10:g.153420077T>C
NC_000023.11:g.154154602T>C
NM_020061.6:c.607T>C MANE Select	NP_064445.2:p.Cys203Arg	missense
NG_009105.2:g.15352T>C

Protein change

C203R

Other names

Canonical SPDI

NC_000023.11:154154601:T:C

Functional consequence

Global minor allele frequency (GMAF)

Allele frequency

Links

ClinGen: CA121104

OMIM: 300822.0003

dbSNP: rs121434621

Aggregate interpretations per condition

Interpreted condition	Interpretation	Number of submissions	Review status	Last evaluated	Variation/condition record
not provided	Pathogenic	1	criteria provided, single submitter	Jul 2, 2015	RCV000479007.1
Cone monochromatism	Pathogenic	1	no assertion criteria provided	Jan 1, 2005	RCV000011251.6

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation viewer	Related variants
Gene	OMIM	HI score Help	TS score Help	Variation viewer	Within gene	All
OPN1LW		-	-	GRCh38 GRCh37	7	250

Submitted interpretations and evidence

Interpretation (Last evaluated)	Review status (Assertion criteria)	Condition (Inheritance)	Submitter	Supporting information (See all)
Pathogenic (Jul 02, 2015)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Allele origin: germline	GeneDx Accession: SCV000566961.2 Submitted: (Jul 13, 2017)	Evidence details Comment: The C203R variant in the OPN1LW gene has been reported previously in association with blue conemonochromatism and Bornholm eye disease (Nathans et al., 1989; Carroll … (more) The C203R variant in the OPN1LW gene has been reported previously in association with blue conemonochromatism and Bornholm eye disease (Nathans et al., 1989; Carroll et al., 2012; Gardner et al., 2014;McClements et al., 2013). The C203R substitution results in misfolded opsins that are retained in the endoplasmicreticulum and degraded, leading to loss of cone ospin function (Kazmi et al., 1997). The C203R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as theseresidues differ in polarity, charge, size and/or other properties. This substitution occurs in the extracellulardomain and is involved in a disulfide bond at a position that is conserved across species. We interpret C203Ras a pathogenic variant. (less)
Pathogenic (Jan 01, 2005)	no assertion criteria provided Method: literature only	BLUE CONE MONOCHROMACY Allele origin: germline	OMIM Accession: SCV000031478.2 Submitted: (Dec 30, 2010)	Evidence details Publications PubMed (2) Nathans, J., Maumenee, I. H., (more...)

Comment:

The C203R variant in the OPN1LW gene has been reported previously in association with blue conemonochromatism and Bornholm eye disease (Nathans et al., 1989; Carroll et al., 2012; Gardner et al., 2014;McClements et al., 2013). The C203R substitution results in misfolded opsins that are retained in the endoplasmicreticulum and degraded, leading to loss of cone ospin function (Kazmi et al., 1997). The C203R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as theseresidues differ in polarity, charge, size and/or other properties. This substitution occurs in the extracellulardomain and is involved in a disulfide bond at a position that is conserved across species. We interpret C203Ras a pathogenic variant.

Functional evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for this variant

Title	Author	Journal	Year	Link
Blue cone monochromatism: a phenotype and genotype assessment with evidence of progressive loss of cone function in older individuals.	Michaelides M	Eye (London, England)	2005	PMID: 15094734
Gene conversion between red and defective green opsin gene in blue cone monochromacy.	Reyniers E	Genomics	1995	PMID: 8666378
Genetic heterogeneity among blue-cone monochromats.	Nathans J	American journal of human genetics	1993	PMID: 8213841
Nathans, J., Maumenee, I. H., Zrenner, E., Sadowski, B., Sharpe, L. T., Lewis, R. A., Hansen, E., Rosenberg, T., Schwartz, M., Heckenlively, J. R., Traboulsi, E., Klingaman, R., Bech-Hansen, N. T., LaRoche, G. R., Pagon, R. A., Murphey, W. H., Weleber, R. G. Genetic heterogeneity among blue-cone monochromats. Am. J. Hum. Genet. 53: 987-1000, 1993.	-	-	-	-

Text-mined citations for rs121434621...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 05, 2020

ClinVar Genomic variation as it relates to human health

NM_020061.6(OPN1LW):c.607T>C (p.Cys203Arg)

NM_020061.6(OPN1LW):c.607T>C (p.Cys203Arg)

Aggregate interpretations per condition

Submitted interpretations and evidence

Functional evidence

Citations for this variant

Text-mined citations for rs121434621...