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NM_201253.3(CRB1):c.1712A>C (p.Glu571Ala) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 26, 2024
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:
RCV004586750.1

Allele description [Variation Report for NM_201253.3(CRB1):c.1712A>C (p.Glu571Ala)]

NM_201253.3(CRB1):c.1712A>C (p.Glu571Ala)

Gene:
CRB1:crumbs cell polarity complex component 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q31.3
Genomic location:
Preferred name:
NM_201253.3(CRB1):c.1712A>C (p.Glu571Ala)
HGVS:
  • NC_000001.11:g.197421540A>C
  • NG_008483.2:g.225079A>C
  • NM_001193640.2:c.1376A>C
  • NM_001257965.2:c.1505A>C
  • NM_001257966.2:c.1712A>C
  • NM_201253.3:c.1712A>CMANE SELECT
  • NP_001180569.1:p.Glu459Ala
  • NP_001244894.1:p.Glu502Ala
  • NP_001244895.1:p.Glu571Ala
  • NP_957705.1:p.Glu571Ala
  • NC_000001.10:g.197390670A>C
  • NM_201253.2:c.1712A>C
  • NR_047563.2:n.1873A>C
  • NR_047564.2:n.1873A>C
Protein change:
E459A
Links:
dbSNP: rs773233587
NCBI 1000 Genomes Browser:
rs773233587
Molecular consequence:
  • NM_001193640.2:c.1376A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257965.2:c.1505A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257966.2:c.1712A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201253.3:c.1712A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_047563.2:n.1873A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_047564.2:n.1873A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005076401Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Apr 26, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]
PMID:
28041643
PMCID:
PMC5223092

Whole-genome sequencing of patients with rare diseases in a national health system.

Turro E, Astle WJ, Megy K, Gräf S, Greene D, Shamardina O, Allen HL, Sanchis-Juan A, Frontini M, Thys C, Stephens J, Mapeta R, Burren OS, Downes K, Haimel M, Tuna S, Deevi SVV, Aitman TJ, Bennett DL, Calleja P, Carss K, Caulfield MJ, et al.

Nature. 2020 Jul;583(7814):96-102. doi: 10.1038/s41586-020-2434-2. Epub 2020 Jun 24.

PubMed [citation]
PMID:
32581362
PMCID:
PMC7610553
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005076401.1

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

Description

Variant summary: CRB1 c.1712A>C (p.Glu571Ala) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251168 control chromosomes. c.1712A>C has been reported in the compound heterozygous state together with a pathogenic variant in the literature in at least 2 individuals affected with inherited retinal dystrophies (e.g. Carss_2017, Daich Varela_2023, Rodriguez_2023, Turro_2020). This variant was also found in trans with a pathogenic variant in one individual with macular dystrophy (age of onset unknown), however age-related macular degeneration was not ruled out (Weisschuh_2024). These data indicate that the variant may be associated with disease. 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: 28041643, 36099972, 37762234, 32581362, 37734845). ClinVar contains an entry for this variant (Variation ID: 438071). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Sep 29, 2024