NM_000527.5(LDLR):c.2375T>C (p.Ile792Thr) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 20, 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:: RCV003372668.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2375T>C (p.Ile792Thr)]

NM_000527.5(LDLR):c.2375T>C (p.Ile792Thr)

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.2375T>C (p.Ile792Thr)

Other names:

NM_000527.5(LDLR):c.2375T>C; p.Ile792Thr

HGVS:

NC_000019.10:g.11128071T>C
NG_009060.1:g.43691T>C
NM_000527.5:c.2375T>CMANE SELECT
NM_001195798.2:c.2375T>C
NM_001195799.2:c.2252T>C
NM_001195800.2:c.1871T>C
NM_001195803.2:c.1841T>C
NP_000518.1:p.Ile792Thr
NP_000518.1:p.Ile792Thr
NP_001182727.1:p.Ile792Thr
NP_001182728.1:p.Ile751Thr
NP_001182729.1:p.Ile624Thr
NP_001182732.1:p.Ile614Thr
LRG_274t1:c.2375T>C
LRG_274:g.43691T>C
LRG_274p1:p.Ile792Thr
NC_000019.9:g.11238747T>C
NM_000527.4:c.2375T>C
c.2375T>C

Protein change:

I614T

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001635; dbSNP: rs764493597

NCBI 1000 Genomes Browser:

rs764493597

Molecular consequence:

NM_000527.5:c.2375T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2375T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.2252T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1871T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1841T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004087580	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 20, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18096825, 19318025, 19446849, 23375686, 27784735 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004087580

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 20, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

Femoral atherosclerosis in heterozygous familial hypercholesterolemia: influence of the genetic defect.

Junyent M, Gilabert R, Zambón D, Pocoví M, Mallén M, Cofán M, Núñez I, Civeira F, Tejedor D, Ros E.

Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):580-6. Epub 2007 Dec 20.

PubMed [citation]

PMID:: 18096825

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P.

Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

PubMed [citation]

PMID:: 19318025

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV004087580.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.I792T variant (also known as c.2375T>C), located in coding exon 16 of the LDLR gene, results from a T to C substitution at nucleotide position 2375. The isoleucine at codon 792 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in familial hypercholesterolemia (FH) cohorts; however, clinical details were limited (Guardamagna O et al. J Pediatr, 2009 Aug;155:199-204.e2; Junyent M et al. Arterioscler Thromb Vasc Biol, 2008 Mar;28:580-6; Alonso R et al. Clin Biochem, 2009 Jun;42:899-903; Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8; Sánchez-Hernández RM et al. Circ Cardiovasc Genet, 2016 Dec;9:504-510). This amino acid position is not well 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.

#	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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