NM_000527.5(LDLR):c.1413_1414delinsGGACAT (p.Gln474fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 23, 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:: RCV003352899.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1413_1414delinsGGACAT (p.Gln474fs)]

NM_000527.5(LDLR):c.1413_1414delinsGGACAT (p.Gln474fs)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1413_1414delinsGGACAT (p.Gln474fs)

HGVS:

NC_000019.10:g.11113589_11113590delinsGGACAT
NG_009060.1:g.29209_29210delinsGGACAT
NM_000527.4:c.1413_1414delAGinsGGACAT
NM_000527.5:c.1413_1414delinsGGACATMANE SELECT
NM_001195798.2:c.1413_1414delinsGGACAT
NM_001195799.2:c.1290_1291delinsGGACAT
NM_001195800.2:c.909_910delinsGGACAT
NM_001195803.2:c.1032_1033delinsGGACAT
NP_000518.1:p.Gln474fs
NP_001182727.1:p.Gln474fs
NP_001182728.1:p.Gln433fs
NP_001182729.1:p.Gln306fs
NP_001182732.1:p.Gln347fs
LRG_274t1:c.1413_1414delAGinsGGACAT
LRG_274:g.29209_29210delinsGGACAT
NC_000019.9:g.11224265_11224266delinsGGACAT

Protein change:

Q306fs

Links:

dbSNP: rs1555805360

NCBI 1000 Genomes Browser:

rs1555805360

Molecular consequence:

NM_000527.5:c.1413_1414delinsGGACAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.1413_1414delinsGGACAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.1290_1291delinsGGACAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.909_910delinsGGACAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1032_1033delinsGGACAT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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PubChem Compound Links for Gene (Select 54059) (16)
PubChem Compound
Homo sapiens ybeY metalloendoribonuclease (YBEY), transcript variant 3, mRNA
Homo sapiens ybeY metalloendoribonuclease (YBEY), transcript variant 3, mRNA
gi|1676440597|ref|NM_001314022.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004053896	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 23, 2023)	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

SCV004053896

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 23, 2023)

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

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study.

Pirillo A, Garlaschelli K, Arca M, Averna M, Bertolini S, Calandra S, Tarugi P, Catapano AL; LIPIGEN Group..

Atheroscler Suppl. 2017 Oct;29:17-24. doi: 10.1016/j.atherosclerosissup.2017.07.002.

PubMed [citation]

PMID:: 28965616

Details of each submission

From Ambry Genetics, SCV004053896.2

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

Description

The c.1413_1414delAGinsGGACAT pathogenic mutation, located in coding exon 10 of the LDLR gene, results from the deletion of two nucleotides and insertion of 6 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.Q474Hfs*63). This variant has been previously reported in a familial hypercholesterolemia (FH) cohort (Pirillo A et al. Atheroscler Suppl, 2017 Oct;29:17-24). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: May 1, 2024

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