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NM_000527.5(LDLR):c.118A>G (p.Ile40Val) AND Familial hypercholesterolemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 18, 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:
RCV001180282.4

Allele description [Variation Report for NM_000527.5(LDLR):c.118A>G (p.Ile40Val)]

NM_000527.5(LDLR):c.118A>G (p.Ile40Val)

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.118A>G (p.Ile40Val)
HGVS:
  • NC_000019.10:g.11100273A>G
  • NG_009060.1:g.15893A>G
  • NM_000527.5:c.118A>GMANE SELECT
  • NM_001195798.2:c.118A>G
  • NM_001195799.2:c.118A>G
  • NM_001195800.2:c.118A>G
  • NM_001195803.2:c.118A>G
  • NP_000518.1:p.Ile40Val
  • NP_000518.1:p.Ile40Val
  • NP_001182727.1:p.Ile40Val
  • NP_001182728.1:p.Ile40Val
  • NP_001182729.1:p.Ile40Val
  • NP_001182732.1:p.Ile40Val
  • LRG_274t1:c.118A>G
  • LRG_274:g.15893A>G
  • LRG_274p1:p.Ile40Val
  • NC_000019.9:g.11210949A>G
  • NM_000527.4:c.118A>G
Protein change:
I40V
Links:
dbSNP: rs765969972
NCBI 1000 Genomes Browser:
rs765969972
Molecular consequence:
  • NM_000527.5:c.118A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.118A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.118A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.118A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.118A>G - 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
SCV001345166Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 18, 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001345166.3

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

Description

This missense variant (also known as p.Ile19Val in the mature protein) replaces isoleucine with valine at codon 40 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related disorders in the literature. This variant has been identified in 3/251276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 1, 2024