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NM_000329.3(RPE65):c.131G>A (p.Arg44Gln) AND RPE65-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 20, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV004528783.1

Allele description [Variation Report for NM_000329.3(RPE65):c.131G>A (p.Arg44Gln)]

NM_000329.3(RPE65):c.131G>A (p.Arg44Gln)

Gene:
RPE65:retinoid isomerohydrolase RPE65 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p31.3
Genomic location:
Preferred name:
NM_000329.3(RPE65):c.131G>A (p.Arg44Gln)
HGVS:
  • NC_000001.11:g.68446824C>T
  • NG_008472.2:g.8136G>A
  • NM_000329.3:c.131G>AMANE SELECT
  • NP_000320.1:p.Arg44Gln
  • NC_000001.10:g.68912507C>T
  • NG_008472.1:g.8136G>A
  • NM_000329.2:c.131G>A
  • Q16518:p.Arg44Gln
  • p.(Arg44Gln)
Protein change:
R44Q
Links:
UniProtKB: Q16518#VAR_017128; dbSNP: rs61751282
NCBI 1000 Genomes Browser:
rs61751282
Molecular consequence:
  • NM_000329.3:c.131G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
RPE65-related disorder
Synonyms:
RPE65-Related Disorders; RPE65-related condition
Identifiers:
MedGen: CN239301

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004109643PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Apr 20, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004109643.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The RPE65 c.131G>A variant is predicted to result in the amino acid substitution p.Arg44Gln. This variant in either homozygous state or along with a second causative variant, has been reported in patients with RPE65-associated disorders such as Leber congenital amaurosis (Simovich et al. 2001. PubMed ID: 11462243; Table S1, Patel. 2016. PubMed ID: 26355662; Cideciyan et al. 2008. PubMed ID: 18809924). Functional in vitro studies have shown that this variant resulted in a protein with reduced isomerization activity (~2% of wild-type activity) (Redmond. 2005. PubMed ID: 16150724; Philp. 2009. PubMed ID: 19431183). This variant is reported in 0.016% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-68912507-C-T). This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024