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NM_001354768.3(NRL):c.152C>T (p.Pro51Leu) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Sep 12, 2022
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:
RCV001172074.27

Allele description [Variation Report for NM_001354768.3(NRL):c.152C>T (p.Pro51Leu)]

NM_001354768.3(NRL):c.152C>T (p.Pro51Leu)

Gene:
NRL:neural retina leucine zipper [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q11.2
Genomic location:
Preferred name:
NM_001354768.3(NRL):c.152C>T (p.Pro51Leu)
HGVS:
  • NC_000014.9:g.24082697G>A
  • NG_011697.2:g.37318C>T
  • NM_001354768.3:c.152C>TMANE SELECT
  • NM_001354769.1:c.152C>T
  • NM_001354770.2:c.66+86C>T
  • NM_006177.5:c.152C>T
  • NP_001341697.1:p.Pro51Leu
  • NP_001341698.1:p.Pro51Leu
  • NP_006168.1:p.Pro51Leu
  • NC_000014.8:g.24551906G>A
  • NC_000014.8:g.24551906G>A
Protein change:
P51L
Links:
dbSNP: rs2036353653
NCBI 1000 Genomes Browser:
rs2036353653
Molecular consequence:
  • NM_001354770.2:c.66+86C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354768.3:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354769.1:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006177.5:c.152C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001335011CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)
Pathogenic
(Mar 1, 2020)
germlineclinical testing

Citation Link,

SCV002196595Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Sep 12, 2022)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function.

Nishiguchi KM, Friedman JS, Sandberg MA, Swaroop A, Berson EL, Dryja TP.

Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17819-24. Epub 2004 Dec 9.

PubMed [citation]
PMID:
15591106
PMCID:
PMC535407

Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity.

Kanda A, Friedman JS, Nishiguchi KM, Swaroop A.

Hum Mutat. 2007 Jun;28(6):589-98.

PubMed [citation]
PMID:
17335001
See all PubMed Citations (5)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001335011.25

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002196595.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro51 amino acid residue in NRL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15591106; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects NRL function (PMID: 17335001). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 916413). This variant is also known as 2316C>T. This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 11385710, 15994872). 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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 51 of the NRL protein (p.Pro51Leu).

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

Last Updated: Oct 20, 2024