NM_000527.5(LDLR):c.126C>A (p.Tyr42Ter) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 2021
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:: RCV001854883.3

Allele description [Variation Report for NM_000527.5(LDLR):c.126C>A (p.Tyr42Ter)]

NM_000527.5(LDLR):c.126C>A (p.Tyr42Ter)

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.126C>A (p.Tyr42Ter)

HGVS:

NC_000019.10:g.11100281C>A
NG_009060.1:g.15901C>A
NM_000527.5:c.126C>AMANE SELECT
NM_001195798.2:c.126C>A
NM_001195799.2:c.126C>A
NM_001195800.2:c.126C>A
NM_001195803.2:c.126C>A
NP_000518.1:p.Tyr42Ter
NP_000518.1:p.Tyr42Ter
NP_001182727.1:p.Tyr42Ter
NP_001182728.1:p.Tyr42Ter
NP_001182729.1:p.Tyr42Ter
NP_001182732.1:p.Tyr42Ter
LRG_274t1:c.126C>A
LRG_274:g.15901C>A
LRG_274p1:p.Tyr42Ter
NC_000019.9:g.11210957C>A
NM_000527.4:c.126C>A
c.126C>A

Protein change:

Y42*

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001385;

Molecular consequence:

NM_000527.5:c.126C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.126C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.126C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.126C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195803.2:c.126C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002239522	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23375686, 28965616, 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002239522

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2021)

germline

clinical testing

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

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 and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

Bertolini S, Pisciotta L, Rabacchi C, Cefalù AB, Noto D, Fasano T, Signori A, Fresa R, Averna M, Calandra S.

Atherosclerosis. 2013 Apr;227(2):342-8. doi: 10.1016/j.atherosclerosis.2013.01.007. Epub 2013 Jan 19.

PubMed [citation]

PMID:: 23375686

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

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002239522.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 251028). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 23375686, 28965616). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr42*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073).

#	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 7, 2024

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