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NM_000527.5(LDLR):c.811G>A (p.Val271Ile) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 23, 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:
RCV003398872.1

Allele description [Variation Report for NM_000527.5(LDLR):c.811G>A (p.Val271Ile)]

NM_000527.5(LDLR):c.811G>A (p.Val271Ile)

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.811G>A (p.Val271Ile)
Other names:
NM_000527.5(LDLR):c.811G>A; p.Val271Ile
HGVS:
  • NC_000019.10:g.11106681G>A
  • NG_009060.1:g.22301G>A
  • NM_000527.5:c.811G>AMANE SELECT
  • NM_001195798.2:c.811G>A
  • NM_001195799.2:c.688G>A
  • NM_001195800.2:c.314-711G>A
  • NM_001195803.2:c.430G>A
  • NP_000518.1:p.Val271Ile
  • NP_001182727.1:p.Val271Ile
  • NP_001182728.1:p.Val230Ile
  • NP_001182732.1:p.Val144Ile
  • LRG_274t1:c.811G>A
  • LRG_274:g.22301G>A
  • NC_000019.9:g.11217357G>A
  • NM_000527.4:c.811G>A
Protein change:
V144I
Links:
dbSNP: rs749220643
NCBI 1000 Genomes Browser:
rs749220643
Molecular consequence:
  • NM_001195800.2:c.314-711G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.811G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.811G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.430G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004121996Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Oct 23, 2023) 		germlineclinical testing

PubMed (4)
[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

Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction.

Brænne I, Kleinecke M, Reiz B, Graf E, Strom T, Wieland T, Fischer M, Kessler T, Hengstenberg C, Meitinger T, Erdmann J, Schunkert H.

Eur J Hum Genet. 2016 Feb;24(2):191-7. doi: 10.1038/ejhg.2015.100. Epub 2015 Jun 3.

PubMed [citation]
PMID:
26036859
PMCID:
PMC4717192

Autosomal dominant hypercholesterolemia in Catalonia: Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting.

Martín-Campos JM, Plana N, Figueras R, Ibarretxe D, Caixàs A, Esteve E, Pérez A, Bueno M, Mauri M, Roig R, Martínez S, Pintó X, Masana L, Julve J, Blanco-Vaca F; Xarxa d’Unitats de Lípids i Arteriosclerosi (XULA)..

J Clin Lipidol. 2018 Nov - Dec;12(6):1452-1462. doi: 10.1016/j.jacl.2018.09.002. Epub 2018 Sep 7.

PubMed [citation]
PMID:
30293936
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004121996.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: LDLR c.811G>A (p.Val271Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251456 control chromosomes. c.811G>A at a heterozygous state has been reported in the literature in several individuals affected with Hypercholesterolemia, or Coronary Aartery Disease and Myocardial Infarction with elevated low-density lipoprotein cholesterollevels (examples, Branne_2016, Huang_2020, Tomar_2022, Martin-Campos_2018). Particularly, Branne_2016 reported this variant in three siblings, two of whom were diagnosed with Coronary Aartery Disease and Myocardial Infarction, and the rest carrier remained unaffected with elevated LDLC levels. However, other studies evaluated this variant insignificant or Likely benign. These report(s) do not provide unequivocal conclusions about association of the variant with autosomal dominant or autosomal recessive Hypercholesterolemia. 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: 26036859, 33994402, 30293936, 35130036). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. 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: Oct 8, 2024