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NM_152443.3(RDH12):c.667G>T (p.Val223Phe) AND Leber congenital amaurosis

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 30, 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:
RCV003399392.1

Allele description [Variation Report for NM_152443.3(RDH12):c.667G>T (p.Val223Phe)]

NM_152443.3(RDH12):c.667G>T (p.Val223Phe)

Genes:
GPHN:gephyrin [Gene - OMIM - HGNC]
RDH12:retinol dehydrogenase 12 [Gene - OMIM - HGNC]
ZFYVE26:zinc finger FYVE-type containing 26 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q24.1
Genomic location:
Preferred name:
NM_152443.3(RDH12):c.667G>T (p.Val223Phe)
HGVS:
  • NC_000014.9:g.67729199G>T
  • NG_008321.1:g.32314G>T
  • NM_152443.3:c.667G>TMANE SELECT
  • NP_689656.2:p.Val223Phe
  • NC_000014.8:g.68195916G>T
Protein change:
V223F
Links:
dbSNP: rs370015375
NCBI 1000 Genomes Browser:
rs370015375
Molecular consequence:
  • NM_152443.3:c.667G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Leber congenital amaurosis (LCA)
Synonyms:
Congenital retinal blindness; Leber's amaurosis
Identifiers:
MONDO: MONDO:0018998; MeSH: D057130; MedGen: C0339527; OMIM: PS204000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004122428Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(Oct 30, 2023)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular Epidemiology in 591 Italian Probands With Nonsyndromic Retinitis Pigmentosa and Usher Syndrome.

Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L.

Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):13. doi: 10.1167/iovs.62.2.13.

PubMed [citation]
PMID:
33576794
PMCID:
PMC7884295

Molecular diagnosis based on comprehensive genetic testing in 800 Chinese families with non-syndromic inherited retinal dystrophies.

Liu X, Tao T, Zhao L, Li G, Yang L.

Clin Exp Ophthalmol. 2021 Jan;49(1):46-59. doi: 10.1111/ceo.13875. Epub 2020 Nov 2.

PubMed [citation]
PMID:
33090715

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004122428.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: RDH12 c.667G>T (p.Val223Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248940 control chromosomes. c.667G>T has been reported in the literature in homozygous individuals affected with Retinitis pigmentosa (Colombo_2021) and Cone-rod dystrophy (Liu_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33576794, 33090715). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Dec 24, 2023