NM_000527.5(LDLR):c.1145G>T (p.Gly382Val) AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 20, 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:: RCV001854901.5

Allele description [Variation Report for NM_000527.5(LDLR):c.1145G>T (p.Gly382Val)]

NM_000527.5(LDLR):c.1145G>T (p.Gly382Val)

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.1145G>T (p.Gly382Val)

HGVS:

NC_000019.10:g.11111598G>T
NG_009060.1:g.27218G>T
NM_000527.5:c.1145G>TMANE SELECT
NM_001195798.2:c.1145G>T
NM_001195799.2:c.1022G>T
NM_001195800.2:c.641G>T
NM_001195803.2:c.764G>T
NP_000518.1:p.Gly382Val
NP_000518.1:p.Gly382Val
NP_001182727.1:p.Gly382Val
NP_001182728.1:p.Gly341Val
NP_001182729.1:p.Gly214Val
NP_001182732.1:p.Gly255Val
LRG_274t1:c.1145G>T
LRG_274:g.27218G>T
LRG_274p1:p.Gly382Val
NC_000019.9:g.11222274G>T
NM_000527.4:c.1145G>T
c.1145G>T

Protein change:

G214V

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001366; dbSNP: rs752951310

NCBI 1000 Genomes Browser:

rs752951310

Molecular consequence:

NM_000527.5:c.1145G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1145G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1022G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.641G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.764G>T - 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
SCV002247986	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 20, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18325082, 23375686, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247986

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 20, 2021)

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

Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database.

Leigh SE, Foster AH, Whittall RA, Hubbart CS, Humphries SE.

Ann Hum Genet. 2008 Jul;72(Pt 4):485-98. doi: 10.1111/j.1469-1809.2008.00436.x. Epub 2008 Mar 5.

PubMed [citation]

PMID:: 18325082

Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

Bertolini S, Pisciotta L, Rabacchi C, Cefalù AB, Noto D, Fasano T, Signori A, Fresa R, Averna M, Calandra S.

Atherosclerosis. 2013 Apr;227(2):342-8. doi: 10.1016/j.atherosclerosis.2013.01.007. Epub 2013 Jan 19.

PubMed [citation]

PMID:: 23375686

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002247986.2

#	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 glycine with valine at codon 382 of the LDLR protein (p.Gly382Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with hypercholesterolemia (PMID: 18325082, 23375686). ClinVar contains an entry for this variant (Variation ID: 251687). 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 disruptive. 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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