NM_000527.5(LDLR):c.196_197del (p.Val66fs) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 27, 2018
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:: RCV000775025.2

Allele description [Variation Report for NM_000527.5(LDLR):c.196_197del (p.Val66fs)]

NM_000527.5(LDLR):c.196_197del (p.Val66fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.196_197del (p.Val66fs)

HGVS:

NC_000019.10:g.11102669_11102670del
NG_009060.1:g.18289_18290del
NM_000527.5:c.196_197delMANE SELECT
NM_001195798.2:c.196_197del
NM_001195799.2:c.190+2324_190+2325del
NM_001195800.2:c.196_197del
NM_001195803.2:c.196_197del
NP_000518.1:p.Val66fs
NP_001182727.1:p.Val66fs
NP_001182729.1:p.Val66fs
NP_001182732.1:p.Val66fs
LRG_274:g.18289_18290del
NC_000019.9:g.11213345_11213346del
NM_000527.4:c.196_197delGT
c.196_197del

Protein change:

V66fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000034; dbSNP: rs875989889

NCBI 1000 Genomes Browser:

rs875989889

Molecular consequence:

NM_000527.5:c.196_197del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.196_197del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.196_197del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.196_197del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.190+2324_190+2325del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Familial hypercholesterolemia
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

Recent activity

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Trgv2 T cell receptor gamma variable 2 [Mus musculus]
Trgv2 T cell receptor gamma variable 2 [Mus musculus]
Gene ID:21636

Gene
Fungal sp. MR53 internal transcribed spacer 1, partial sequence; 5.8S ribosomal ...
Fungal sp. MR53 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene and internal transcribed spacer 2, complete sequence; and 28S ribosomal RNA gene, partial sequence
gi|159034031|gb|EU222997.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000909122	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 27, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000909122

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 27, 2018)

germline

clinical testing

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000909122.1

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

Description

Pathogenic variant based on current evidence: This variant deletes two nucleotides in exon 3 of the LDLR gene. This creates a frameshift and premature translational stop signal and is expected to result in an absent or non-functional protein product. This variant has been reported in an Australian individual affected with familial hypercholesterolemia (PMID: 22883975). This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Truncating variants in LDLR are known to be pathogenic (PMID: 20809525). Based on available evidence, this variant is classified as Pathogenic.

#	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 1, 2024

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