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NM_000527.5(LDLR):c.1738T>C (p.Ser580Pro) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 7, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000417299.3

Allele description [Variation Report for NM_000527.5(LDLR):c.1738T>C (p.Ser580Pro)]

NM_000527.5(LDLR):c.1738T>C (p.Ser580Pro)

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.1738T>C (p.Ser580Pro)
Other names:
NM_000527.5(LDLR):c.1738T>C
HGVS:
  • NC_000019.10:g.11116891T>C
  • NG_009060.1:g.32511T>C
  • NM_000527.5:c.1738T>CMANE SELECT
  • NM_001195798.2:c.1738T>C
  • NM_001195799.2:c.1615T>C
  • NM_001195800.2:c.1234T>C
  • NM_001195803.2:c.1357T>C
  • NP_000518.1:p.Ser580Pro
  • NP_000518.1:p.Ser580Pro
  • NP_001182727.1:p.Ser580Pro
  • NP_001182728.1:p.Ser539Pro
  • NP_001182729.1:p.Ser412Pro
  • NP_001182732.1:p.Ser453Pro
  • LRG_274t1:c.1738T>C
  • LRG_274:g.32511T>C
  • LRG_274p1:p.Ser580Pro
  • NC_000019.9:g.11227567T>C
  • NM_000527.4:c.1738T>C
Protein change:
S412P
Links:
dbSNP: rs1057519675
NCBI 1000 Genomes Browser:
rs1057519675
Molecular consequence:
  • NM_000527.5:c.1738T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1738T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1615T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1234T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hypercholesterolemia, familial, 1
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000503405Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Dec 16, 2016) 		germlineclinical testing

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

SCV005328522ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain Significance
(Nov 7, 2023) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedgermlineyes1not providednot provided2600not 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 Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503405.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

subject mutated among 2600 FH index cases screened = 1/Software predictions: Conflicting

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes2600not providednot provided1not providednot providednot provided

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV005328522.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5(LDLR):c.1738T>C (p.Ser580Pro) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP3 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 7 November 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL=0.911. PP4: Variant meets PM2 and is identified in 1 index case with possible FH by Simon Broome criteria from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, France, after alternative causes of high cholesterol were excluded.

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

Last Updated: Oct 8, 2024