NM_000527.5(LDLR):c.1414G>T (p.Asp472Tyr) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Aug 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000161988.16

Allele description [Variation Report for NM_000527.5(LDLR):c.1414G>T (p.Asp472Tyr)]

NM_000527.5(LDLR):c.1414G>T (p.Asp472Tyr)

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.1414G>T (p.Asp472Tyr)

HGVS:

NC_000019.10:g.11113590G>T
NG_009060.1:g.29210G>T
NM_000527.5:c.1414G>TMANE SELECT
NM_001195798.2:c.1414G>T
NM_001195799.2:c.1291G>T
NM_001195800.2:c.910G>T
NM_001195803.2:c.1033G>T
NP_000518.1:p.Asp472Tyr
NP_000518.1:p.Asp472Tyr
NP_001182727.1:p.Asp472Tyr
NP_001182728.1:p.Asp431Tyr
NP_001182729.1:p.Asp304Tyr
NP_001182732.1:p.Asp345Tyr
LRG_274t1:c.1414G>T
LRG_274:g.29210G>T
LRG_274p1:p.Asp472Tyr
NC_000019.9:g.11224266G>T
NM_000527.4:c.1414G>T
NM_000527.5:c.1414G>T
c.1414G>T
p.(Asp472Tyr)
p.D472Y

Protein change:

D304Y

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000886; dbSNP: rs730882102

NCBI 1000 Genomes Browser:

rs730882102

Molecular consequence:

NM_000527.5:c.1414G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1414G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1291G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.910G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1033G>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functional variant [Sequence Ontology: SO:0001536] - Comment(s)

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189563	Dept. of Genetics and Pharmacogenomics, Merck Research Labs	no classification provided (in vitro)	not provided	not applicable	in vitro	PubMed (1) [See all records that cite this PMID]
SCV000234649	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 22, 2016)	germline	clinical testing	Citation Link,
SCV000888161	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely pathogenic (May 4, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004227678	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 7, 2022)	germline	clinical testing	PubMed (16) [See all records that cite these PMIDs] 17196209, 21310417, 22698793, 23375686, 25487149, 25647241, 27542166, 27824480, 28008010, 28161202, 31447099, 31980526, 32977124, 34297352, 34379075, 25741868
SCV005329923	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Aug 1, 2024)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Detection of familial hypercholesterolemia in a cohort of children with hypercholesterolemia: results of a family and DNA-based screening.

Campagna F, Martino F, Bifolco M, Montali A, Martino E, Morrone F, Antonini R, Cantafora A, Verna R, Arca M.

Atherosclerosis. 2008 Jan;196(1):356-364. doi: 10.1016/j.atherosclerosis.2006.11.015. Epub 2006 Dec 28.

PubMed [citation]

PMID:: 17196209

See all PubMed Citations (17)

Details of each submission

From Dept. of Genetics and Pharmacogenomics, Merck Research Labs, SCV000189563.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

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

From GeneDx, SCV000234649.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The D472Y c.1414 GAC>TAC variant in the LDLR gene has been published previously as a disease-causing variant in association with hypercholesterolemia (Campagna et al., 2008; Bertolini et al., 2013). Based on the ACMG recommendations, D472Y is interpreted as a known pathogenic sequence change.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888161.2

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

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004227678.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (16)

Description

PP1, PM2_supporting, PM3, PS3_supporting, PS4

#	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		1	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV005329923.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

LDLR: PP1:Strong, PM2, PM5, PS4:Moderate, PS3:Supporting

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

Last Updated: Nov 30, 2024

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