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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 27, 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:: RCV002321911.2

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)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002609020	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 27, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15998910, 26345093, 9137885 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002609020

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 27, 2021)

germline

clinical testing

PubMed (3)
[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

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

Screening for genetic mutations in LDLR gene with familial hypercholesterolemia patients in the Saudi population.

Alharbi KK, Kashour TS, Al-Hussaini W, Nbaheen MS, Hasanato RM, Mohamed S, Tamimi W, Khan IA.

Acta Biochim Pol. 2015;62(3):559-62. doi: 10.18388/abp.2015_1015. Epub 2015 Sep 8.

PubMed [citation]

PMID:: 26345093

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002609020.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.313C>T variant (also known as p.P105S), located in coding exon 3 of the LDLR gene, results from a C to T substitution at nucleotide position 313. The amino acid change results in proline to serine at codon 105, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 3, which makes it likely to have some effect on normal mRNA splicing. This alteration has been reported in association with familial hypercholesterolemia (FH) (Vuorio AF et al. Clin Genet, 1997 Mar;51:191-5; Alharbi KK et al. Genome Res, 2005 Jul;15:967-77). This nucleotide and amino acid positions are poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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