NM_000527.5(LDLR):c.1817C>A (p.Ala606Asp) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 31, 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:: RCV002413393.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1817C>A (p.Ala606Asp)]

NM_000527.5(LDLR):c.1817C>A (p.Ala606Asp)

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.1817C>A (p.Ala606Asp)

Other names:

NM_000527.5(LDLR):c.1817C>A; p.Ala606Asp

HGVS:

NC_000019.10:g.11116970C>A
NG_009060.1:g.32590C>A
NM_000527.5:c.1817C>AMANE SELECT
NM_001195798.2:c.1817C>A
NM_001195799.2:c.1694C>A
NM_001195800.2:c.1313C>A
NM_001195803.2:c.1436C>A
NP_000518.1:p.Ala606Asp
NP_000518.1:p.Ala606Asp
NP_001182727.1:p.Ala606Asp
NP_001182728.1:p.Ala565Asp
NP_001182729.1:p.Ala438Asp
NP_001182732.1:p.Ala479Asp
LRG_274t1:c.1817C>A
LRG_274:g.32590C>A
LRG_274p1:p.Ala606Asp
NC_000019.9:g.11227646C>A
NM_000527.4:c.1817C>A

Protein change:

A438D

Links:

dbSNP: rs1410295777

NCBI 1000 Genomes Browser:

rs1410295777

Molecular consequence:

NM_000527.5:c.1817C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1817C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1694C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1313C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1436C>A - 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
SCV002714123	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 31, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002714123

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 31, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Population genetic screening efficiently identifies carriers of autosomal dominant diseases.

Grzymski JJ, Elhanan G, Morales Rosado JA, Smith E, Schlauch KA, Read R, Rowan C, Slotnick N, Dabe S, Metcalf WJ, Lipp B, Reed H, Sharma L, Levin E, Kao J, Rashkin M, Bowes J, Dunaway K, Slonim A, Washington N, Ferber M, Bolze A, et al.

Nat Med. 2020 Aug;26(8):1235-1239. doi: 10.1038/s41591-020-0982-5. Epub 2020 Jul 27.

PubMed [citation]

PMID:: 32719484

Details of each submission

From Ambry Genetics, SCV002714123.2

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

Description

The p.A606D variant (also known as c.1817C>A), located in coding exon 12 of the LDLR gene, results from a C to A substitution at nucleotide position 1817. The alanine at codon 606 is replaced by aspartic acid, an amino acid with dissimilar properties. This alteration was detected in a cohort of 29,906 healthy individuals who underwent multigene panel testing (Grzymski JJ et al. Nat Med, 2020 08;26:1235-1239). This amino acid position is 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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