NM_000527.5(LDLR):c.1723C>T (p.Leu575Phe) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 12, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001509013.7

Allele description [Variation Report for NM_000527.5(LDLR):c.1723C>T (p.Leu575Phe)]

NM_000527.5(LDLR):c.1723C>T (p.Leu575Phe)

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.1723C>T (p.Leu575Phe)

HGVS:

NC_000019.10:g.11116876C>T
NG_009060.1:g.32496C>T
NM_000527.5:c.1723C>TMANE SELECT
NM_001195798.2:c.1723C>T
NM_001195799.2:c.1600C>T
NM_001195800.2:c.1219C>T
NM_001195803.2:c.1342C>T
NP_000518.1:p.Leu575Phe
NP_000518.1:p.Leu575Phe
NP_001182727.1:p.Leu575Phe
NP_001182728.1:p.Leu534Phe
NP_001182729.1:p.Leu407Phe
NP_001182732.1:p.Leu448Phe
LRG_274t1:c.1723C>T
LRG_274:g.32496C>T
LRG_274p1:p.Leu575Phe
NC_000019.9:g.11227552C>T
NM_000527.4(LDLR):c.1723C>T
NM_000527.4:c.1723C>T
p.Leu575Phe

Protein change:

L407F

Links:

dbSNP: rs1205480064

NCBI 1000 Genomes Browser:

rs1205480064

Molecular consequence:

NM_000527.5:c.1723C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1723C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1600C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1219C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1342C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001715495	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 13, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003918409	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jan 12, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001715495

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 13, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003918409

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Jan 12, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Details of each submission

From Mayo Clinic Laboratories, Mayo Clinic, SCV001715495.1

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

From GeneDx, SCV003918409.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest a damaging effect on protein function (Jiang et al., 2016); This variant is associated with the following publications: (PMID: 29874871, 32041611, 33994402, 27830735, 33747976)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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