NM_000527.5(LDLR):c.313C>T (p.Pro105Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 12, 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:: RCV000781506.1

Allele description [Variation Report for NM_000527.5(LDLR):c.313C>T (p.Pro105Ser)]

NM_000527.5(LDLR):c.313C>T (p.Pro105Ser)

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.313C>T (p.Pro105Ser)

HGVS:

NC_000019.10:g.11102786C>T
NG_009060.1:g.18406C>T
NM_000527.5:c.313C>TMANE SELECT
NM_001195798.2:c.313C>T
NM_001195799.2:c.191-2434C>T
NM_001195800.2:c.313C>T
NM_001195803.2:c.313C>T
NP_000518.1:p.Pro105Ser
NP_000518.1:p.Pro105Ser
NP_001182727.1:p.Pro105Ser
NP_001182729.1:p.Leu105=
NP_001182732.1:p.Pro105Ser
LRG_274t1:c.313C>T
LRG_274:g.18406C>T
LRG_274p1:p.Pro105Ser
NC_000019.9:g.11213462C>T
NM_000527.4:c.313C>T
c.313C>T

Protein change:

P105S

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000442; dbSNP: rs13306510

NCBI 1000 Genomes Browser:

rs13306510

Molecular consequence:

NM_001195799.2:c.191-2434C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.313C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.313C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.313C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.313C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000919588	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 12, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18607183, 15998910 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000919588

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 12, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?

Humphries SE, Norbury G, Leigh S, Hadfield SG, Nair D.

Curr Opin Lipidol. 2008 Aug;19(4):362-8. doi: 10.1097/MOL.0b013e32830636e5. Review.

PubMed [citation]

PMID:: 18607183

Mutation scanning by meltMADGE: validations using BRCA1 and LDLR, and demonstration of the potential to identify severe, moderate, silent, rare, and paucimorphic mutations in the general population.

Alharbi KK, Aldahmesh MA, Spanakis E, Haddad L, Whittall RA, Chen XH, Rassoulian H, Smith MJ, Sillibourne J, Ball NJ, Graham NJ, Briggs PJ, Simpson IA, Phillips DI, Lawlor DA, Ye S, Humphries SE, Cooper C, Smith GD, Ebrahim S, Eccles DM, Day IN.

Genome Res. 2005 Jul;15(7):967-77.

PubMed [citation]

PMID:: 15998910
PMCID:: PMC1172041

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919588.1

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

Description

Variant summary: LDLR c.313C>T (p.Pro105Ser) results in a non-conservative amino acid change located in the Low-density lipoprotein (LDL) receptor class A repeat region of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.4e-05 in 277426 control chromosomes (gnomAD and publication). This frequency is not significantly higher than expected for a pathogenic variant in LDLR causing Familial Hypercholesterolemia (9.4e-05 vs 0.0013), allowing no conclusion about variant significance. c.313C>T has been reported in the literature in individuals affected with Familial Hypercholesterolemia including a family that suggests lack of cosegregation with disease (Vuorio_1997). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

#	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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