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NM_201253.3(CRB1):c.2963T>C (p.Ile988Thr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 1, 2021
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:
RCV001315672.7

Allele description [Variation Report for NM_201253.3(CRB1):c.2963T>C (p.Ile988Thr)]

NM_201253.3(CRB1):c.2963T>C (p.Ile988Thr)

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.2963T>C (p.Ile988Thr)
HGVS:
  • NC_000001.11:g.197434826T>C
  • NG_008483.2:g.238365T>C
  • NM_001193640.2:c.2627T>C
  • NM_001257965.2:c.2891T>C
  • NM_001257966.2:c.2129-774T>C
  • NM_201253.3:c.2963T>CMANE SELECT
  • NP_001180569.1:p.Ile876Thr
  • NP_001244894.1:p.Ile964Thr
  • NP_957705.1:p.Ile988Thr
  • NC_000001.10:g.197403956T>C
  • NR_047563.2:n.2916T>C
  • NR_047564.2:n.3124T>C
Protein change:
I876T
Links:
dbSNP: rs1571555801
NCBI 1000 Genomes Browser:
rs1571555801
Molecular consequence:
  • NM_001257966.2:c.2129-774T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001193640.2:c.2627T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257965.2:c.2891T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_201253.3:c.2963T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_047563.2:n.2916T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_047564.2:n.3124T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Retinitis pigmentosa 12 (RP12)
Synonyms:
RP 12; RP WITH OR WITHOUT PPRPE; RP WITH OR WITHOUT PRESERVED PARAARTERIOLE RETINAL PIGMENT EPITHELIUM; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010818; MedGen: C1838647; Orphanet: 791; OMIM: 600105
Name:
Leber congenital amaurosis 8 (LCA8)
Identifiers:
MONDO: MONDO:0013453; MedGen: C3151202; Orphanet: 65; OMIM: 613835

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001506259Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Sep 1, 2021)
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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001506259.4

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

Description

This sequence change replaces isoleucine with threonine at codon 988 of the CRB1 protein (p.Ile988Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CRB1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CRB1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024