NM_000527.5(LDLR):c.451G>C (p.Ala151Pro) AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 2022
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:: RCV002518476.2

Allele description [Variation Report for NM_000527.5(LDLR):c.451G>C (p.Ala151Pro)]

NM_000527.5(LDLR):c.451G>C (p.Ala151Pro)

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.451G>C (p.Ala151Pro)

HGVS:

NC_000019.10:g.11105357G>C
NG_009060.1:g.20977G>C
NM_000527.5:c.451G>CMANE SELECT
NM_001195798.2:c.451G>C
NM_001195799.2:c.328G>C
NM_001195800.2:c.314-2035G>C
NM_001195803.2:c.314-1208G>C
NP_000518.1:p.Ala151Pro
NP_000518.1:p.Ala151Pro
NP_001182727.1:p.Ala151Pro
NP_001182728.1:p.Ala110Pro
LRG_274t1:c.451G>C
LRG_274:g.20977G>C
LRG_274p1:p.Ala151Pro
NC_000019.9:g.11216033G>C
NM_000527.4:c.451G>C
c.451G>C

Protein change:

A110P

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000917; dbSNP: rs763233960

NCBI 1000 Genomes Browser:

rs763233960

Molecular consequence:

NM_001195800.2:c.314-2035G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1208G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.451G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.451G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.328G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003259877	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11642133, 16792510, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003259877

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Four new mutations and polymorphic variants of the low density lipoprotein receptor in patients with familial hypercholesterolemia in Saint Petersburg].

Tatishcheva IuA, Mandel'shtam MIu, Golubkov VI, Lipovetskiĭ BM, Gaĭtskhoki VS.

Genetika. 2001 Sep;37(9):1290-5. Russian.

PubMed [citation]

PMID:: 11642133

Molecular genetic testing for familial hypercholesterolemia in the Netherlands: a stepwise screening strategy enhances the mutation detection rate.

Lombardi MP, Redeker EJ, van Gent DH, Smeele KL, Weerdesteijn R, Mannens MM.

Genet Test. 2006 Summer;10(2):77-84.

PubMed [citation]

PMID:: 16792510

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003259877.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 151 of the LDLR protein (p.Ala151Pro). This variant is present in population databases (rs763233960, gnomAD 0.003%). This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 11642133, 16792510; Invitae). This variant is also known as p.Ala130Pro. ClinVar contains an entry for this variant (Variation ID: 251234). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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