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NM_000527.5(LDLR):c.511C>A (p.Pro171Thr) AND Familial hypercholesterolemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 12, 2021
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:
RCV002908524.2

Allele description [Variation Report for NM_000527.5(LDLR):c.511C>A (p.Pro171Thr)]

NM_000527.5(LDLR):c.511C>A (p.Pro171Thr)

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.511C>A (p.Pro171Thr)
HGVS:
  • NC_000019.10:g.11105417C>A
  • NG_009060.1:g.21037C>A
  • NG_140410.1:g.634C>A
  • NM_000527.5:c.511C>AMANE SELECT
  • NM_001195798.2:c.511C>A
  • NM_001195799.2:c.388C>A
  • NM_001195800.2:c.314-1975C>A
  • NM_001195803.2:c.314-1148C>A
  • NP_000518.1:p.Pro171Thr
  • NP_000518.1:p.Pro171Thr
  • NP_001182727.1:p.Pro171Thr
  • NP_001182728.1:p.Pro130Thr
  • LRG_274t1:c.511C>A
  • LRG_274:g.21037C>A
  • LRG_274p1:p.Pro171Thr
  • NC_000019.9:g.11216093C>A
  • NM_000527.4:c.511C>A
Protein change:
P130T
Molecular consequence:
  • NM_001195800.2:c.314-1975C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1148C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.511C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.511C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.388C>A - 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
SCV003249554Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 12, 2021) 		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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003249554.1

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

Description

This sequence change replaces proline with threonine at codon 171 of the LDLR protein (p.Pro171Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LDLR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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

Last Updated: Sep 29, 2024