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NM_000527.5(LDLR):c.248T>C (p.Ile83Thr) AND Familial hypercholesterolemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 17, 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:
RCV003766887.2

Allele description [Variation Report for NM_000527.5(LDLR):c.248T>C (p.Ile83Thr)]

NM_000527.5(LDLR):c.248T>C (p.Ile83Thr)

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.248T>C (p.Ile83Thr)
HGVS:
  • NC_000019.10:g.11102721T>C
  • NG_009060.1:g.18341T>C
  • NM_000527.5:c.248T>CMANE SELECT
  • NM_001195798.2:c.248T>C
  • NM_001195799.2:c.190+2376T>C
  • NM_001195800.2:c.248T>C
  • NM_001195803.2:c.248T>C
  • NP_000518.1:p.Ile83Thr
  • NP_000518.1:p.Ile83Thr
  • NP_001182727.1:p.Ile83Thr
  • NP_001182729.1:p.Ile83Thr
  • NP_001182732.1:p.Ile83Thr
  • LRG_274t1:c.248T>C
  • LRG_274:g.18341T>C
  • LRG_274p1:p.Ile83Thr
  • NC_000019.9:g.11213397T>C
  • NM_000527.4:c.248T>C
Protein change:
I83T
Links:
dbSNP: rs1555802745
NCBI 1000 Genomes Browser:
rs1555802745
Molecular consequence:
  • NM_001195799.2:c.190+2376T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hypercholesterolemia
Identifiers:
MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004659136Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 17, 2023) 		germlineclinical testing

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

Help

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, SCV004659136.1

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 83 of the LDLR protein (p.Ile83Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. ClinVar contains an entry for this variant (Variation ID: 440551). 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 expected to disrupt LDLR 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