NM_000527.5(LDLR):c.1708CTC[1] (p.Leu571del) AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 14, 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:: RCV003832914.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1708CTC[1] (p.Leu571del)]

NM_000527.5(LDLR):c.1708CTC[1] (p.Leu571del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1708CTC[1] (p.Leu571del)

HGVS:

NC_000019.10:g.11116861CTC[1]
NG_009060.1:g.32481CTC[1]
NM_000527.5:c.1708CTC[1]MANE SELECT
NM_001195798.2:c.1708CTC[1]
NM_001195799.2:c.1585CTC[1]
NM_001195800.2:c.1204CTC[1]
NM_001195803.2:c.1327CTC[1]
NP_000518.1:p.Leu571del
NP_000518.1:p.Leu571del
NP_001182727.1:p.Leu571del
NP_001182728.1:p.Leu530del
NP_001182729.1:p.Leu403del
NP_001182732.1:p.Leu444del
LRG_274t1:c.1708_1710CTC[1]
LRG_274:g.32481CTC[1]
LRG_274p1:p.Leu571del
NC_000019.9:g.11227537CTC[1]
NC_000019.9:g.11227537_11227539del
NM_000527.4:c.1708_1710CTC[1]

Protein change:

L403del

Molecular consequence:

NM_000527.5:c.1708CTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195798.2:c.1708CTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195799.2:c.1585CTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195800.2:c.1204CTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195803.2:c.1327CTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

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

Recent activity

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Hypergammaglobulinemia
Hypergammaglobulinemia
An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.<br/>Year introduced: 1972(1969)

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004630308	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33418990, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004630308

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 14, 2023)

germline

clinical testing

PubMed (2)
[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

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia.

Meshkov A, Ershova A, Kiseleva A, Zotova E, Sotnikova E, Petukhova A, Zharikova A, Malyshev P, Rozhkova T, Blokhina A, Limonova A, Ramensky V, Divashuk M, Khasanova Z, Bukaeva A, Kurilova O, Skirko O, Pokrovskaya M, Mikova V, Snigir E, Akinshina A, Mitrofanov S, et al.

Genes (Basel). 2021 Jan 6;12(1). doi:pii: 66. 10.3390/genes12010066.

PubMed [citation]

PMID:: 33418990
PMCID:: PMC7825309

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004630308.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 33418990; Invitae). This variant is present in population databases (rs772492150, gnomAD 0.02%). This variant, c.1711_1713del, results in the deletion of 1 amino acid(s) of the LDLR protein (p.Leu571del), but otherwise preserves the integrity of the reading frame.

#	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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