NM_000527.4(LDLR):c.861C>T (p.Gly287=) AND Familial hypercholesterolemia

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jul 27, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000698309.3

Allele description [Variation Report for NM_000527.4(LDLR):c.861C>T (p.Gly287=)]

NM_000527.4(LDLR):c.861C>T (p.Gly287=)

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.4(LDLR):c.861C>T (p.Gly287=)
HGVS:
  • NC_000019.10:g.11107435C>T
  • NG_009060.1:g.23055C>T
  • NM_000527.4:c.861C>T
  • NM_001195798.2:c.861C>T
  • NM_001195799.2:c.738C>T
  • NM_001195800.2:c.357C>T
  • NM_001195803.2:c.480C>T
  • NP_000518.1:p.Gly287=
  • NP_001182727.1:p.Gly287=
  • NP_001182728.1:p.Gly246=
  • NP_001182729.1:p.Gly119=
  • NP_001182732.1:p.Gly160=
  • LRG_274t1:c.861C>T
  • LRG_274:g.23055C>T
  • LRG_274p1:p.Gly287=
  • NC_000019.9:g.11218111C>T
Links:
dbSNP: rs770191650
NCBI 1000 Genomes Browser:
rs770191650
Molecular consequence:
  • NM_000527.4:c.861C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195798.2:c.861C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195799.2:c.738C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195800.2:c.357C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001195803.2:c.480C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000826969Invitaecriteria provided, single submitter
Uncertain significance
(Jul 3, 2018)
germlineclinical testing

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

SCV001359440Color Health, Inccriteria provided, single submitter
Likely benign
(Jul 27, 2019)
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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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 Invitae, SCV000826969.2

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

Description

This sequence change affects codon 287 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDLR protein. This variant is present in population databases (rs770191650, ExAC 0.02%). This variant has not been reported in the literature in individuals with LDLR-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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

From Color Health, Inc, SCV001359440.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 12, 2021

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