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NM_000527.5(LDLR):c.1822C>T (p.Pro608Ser) AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 10, 2022
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:
RCV003114411.5

Allele description [Variation Report for NM_000527.5(LDLR):c.1822C>T (p.Pro608Ser)]

NM_000527.5(LDLR):c.1822C>T (p.Pro608Ser)

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.1822C>T (p.Pro608Ser)
HGVS:
  • NC_000019.10:g.11116975C>T
  • NG_009060.1:g.32595C>T
  • NM_000527.5:c.1822C>TMANE SELECT
  • NM_001195798.2:c.1822C>T
  • NM_001195799.2:c.1699C>T
  • NM_001195800.2:c.1318C>T
  • NM_001195803.2:c.1441C>T
  • NP_000518.1:p.Pro608Ser
  • NP_000518.1:p.Pro608Ser
  • NP_001182727.1:p.Pro608Ser
  • NP_001182728.1:p.Pro567Ser
  • NP_001182729.1:p.Pro440Ser
  • NP_001182732.1:p.Pro481Ser
  • LRG_274t1:c.1822C>T
  • LRG_274:g.32595C>T
  • LRG_274p1:p.Pro608Ser
  • NC_000019.9:g.11227651C>T
  • NM_000527.4:c.1822C>T
  • NM_000527.5:c.1822C>T
  • P01130:p.Pro608Ser
  • c.1822C>T
Protein change:
P440S
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000662; UniProtKB: P01130#VAR_007989; dbSNP: rs879255034
NCBI 1000 Genomes Browser:
rs879255034
Molecular consequence:
  • NM_000527.5:c.1822C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1822C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1699C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1318C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1441C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003790374Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 10, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003790374.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro608 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 9544745, 11313767), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 252049). This variant is also known as P587S. This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 9852677, 21310417). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 608 of the LDLR protein (p.Pro608Ser).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024