NM_000527.5(LDLR):c.2177C>T (p.Thr726Ile) AND Familial hypercholesterolemia

Germline classification:: Benign (5 submissions)
Last evaluated:: Jan 31, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000771082.18

Allele description [Variation Report for NM_000527.5(LDLR):c.2177C>T (p.Thr726Ile)]

NM_000527.5(LDLR):c.2177C>T (p.Thr726Ile)

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.2177C>T (p.Thr726Ile)

Other names:

FH Paris-9; NM_000527.5(LDLR):c.2177C>T

HGVS:

NC_000019.10:g.11123210C>T
NG_009060.1:g.38830C>T
NM_000527.5:c.2177C>TMANE SELECT
NM_001195798.2:c.2177C>T
NM_001195799.2:c.2054C>T
NM_001195800.2:c.1673C>T
NM_001195803.2:c.1643C>T
NP_000518.1:p.Thr726Ile
NP_000518.1:p.Thr726Ile
NP_001182727.1:p.Thr726Ile
NP_001182728.1:p.Thr685Ile
NP_001182729.1:p.Thr558Ile
NP_001182732.1:p.Thr548Ile
LRG_274t1:c.2177C>T
LRG_274:g.38830C>T
LRG_274p1:p.Thr726Ile
NC_000019.9:g.11233886C>T
NM_000527.4:c.2177C>T
P01130:p.Thr726Ile
c.2177C>T

Protein change:

T548I

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001613; UniProtKB: P01130#VAR_005413

Molecular consequence:

NM_000527.5:c.2177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.2054C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1643C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

no known functional consequence - Comment(s)

Condition(s)

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

Recent activity

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21686[HGNC] (215)
ClinVar
tgt [Brucella melitensis bv. 1 str. 16M]
tgt [Brucella melitensis bv. 1 str. 16M]
Gene ID:29593705

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000556773	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000689774	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jan 19, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000902622	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jun 28, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001453900	Natera, Inc.	no assertion criteria provided	Benign (Jan 12, 2020)	germline	clinical testing
SCV005050216	GENinCode PLC	criteria provided, single submitter (Chora et al. (Genet Med. 2022))	Benign (Aug 10, 2022)	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

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

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000556773.9

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

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000689774.3

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

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000902622.1

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

#	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

From Natera, Inc., SCV001453900.1

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

#	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

From GENinCode PLC, SCV005050216.1

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

#	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: Nov 10, 2024

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