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NM_000527.5(LDLR):c.1945C>T (p.Pro649Ser) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 19, 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:
RCV003372665.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1945C>T (p.Pro649Ser)]

NM_000527.5(LDLR):c.1945C>T (p.Pro649Ser)

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.1945C>T (p.Pro649Ser)
HGVS:
  • NC_000019.10:g.11120191C>T
  • NG_009060.1:g.35811C>T
  • NM_000527.4:c.1945C>T
  • NM_000527.5:c.1945C>TMANE SELECT
  • NM_001195798.2:c.1945C>T
  • NM_001195799.2:c.1822C>T
  • NM_001195800.2:c.1441C>T
  • NM_001195803.2:c.1564C>T
  • NP_000518.1:p.Pro649Ser
  • NP_001182727.1:p.Pro649Ser
  • NP_001182728.1:p.Pro608Ser
  • NP_001182729.1:p.Pro481Ser
  • NP_001182732.1:p.Pro522Ser
  • LRG_274t1:c.1945C>T
  • LRG_274:g.35811C>T
  • NC_000019.9:g.11230867C>T
  • c.1945C>T
Protein change:
P481S
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001558; dbSNP: rs879255080
NCBI 1000 Genomes Browser:
rs879255080
Molecular consequence:
  • NM_000527.5:c.1945C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1945C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1822C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1441C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1564C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004087547Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Uncertain significance
(Jul 19, 2023)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network., Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]
PMID:
20809525
PMCID:
PMC3152176

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia.

Meshkov A, Ershova A, Kiseleva A, Zotova E, Sotnikova E, Petukhova A, Zharikova A, Malyshev P, Rozhkova T, Blokhina A, Limonova A, Ramensky V, Divashuk M, Khasanova Z, Bukaeva A, Kurilova O, Skirko O, Pokrovskaya M, Mikova V, Snigir E, Akinshina A, Mitrofanov S, et al.

Genes (Basel). 2021 Jan 6;12(1). doi:pii: 66. 10.3390/genes12010066.

PubMed [citation]
PMID:
33418990
PMCID:
PMC7825309

Details of each submission

From Ambry Genetics, SCV004087547.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.P649S variant (also known as c.1945C>T), located in coding exon 13 of the LDLR gene, results from a C to T substitution at nucleotide position 1945. The proline at codon 649 is replaced by serine, an amino acid with similar properties. This alteration has been reported in familial hypercholesterolemia (FH) cohorts (Marduel M et al. Hum Mutat, 2010 Nov;31:E1811-24; Meshkov A et al. Genes (Basel), 2021 Jan;12:). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Sep 29, 2024