NM_003383.5(VLDLR):c.242A>G (p.Asn81Ser) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Benign(1);Likely benign(1);Uncertain significance(1) (Last evaluated: Jun 9, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000498823.1

Allele description [Variation Report for NM_003383.5(VLDLR):c.242A>G (p.Asn81Ser)]

NM_003383.5(VLDLR):c.242A>G (p.Asn81Ser)

Gene:
VLDLR:very low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9p24.2
Genomic location:
Preferred name:
NM_003383.5(VLDLR):c.242A>G (p.Asn81Ser)
HGVS:
  • NC_000009.12:g.2639898A>G
  • NG_012741.1:g.23106A>G
  • NM_001018056.3:c.242A>G
  • NM_001322225.2:c.242A>G
  • NM_001322226.2:c.242A>G
  • NM_003383.5:c.242A>GMANE SELECT
  • NP_001018066.1:p.Asn81Ser
  • NP_001309154.1:p.Asn81Ser
  • NP_001309155.1:p.Asn81Ser
  • NP_003374.3:p.Asn81Ser
  • NC_000009.11:g.2639898A>G
  • NM_003383.3:c.242A>G
  • NM_003383.4:c.242A>G
Protein change:
N81S
Links:
dbSNP: rs140526335
NCBI 1000 Genomes Browser:
rs140526335
Molecular consequence:
  • NM_001018056.3:c.242A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322225.2:c.242A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322226.2:c.242A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003383.5:c.242A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000589445GeneDxcriteria provided, single submitter
Uncertain significance
(Jun 9, 2017)
germlineclinical testing

Citation Link,

SCV000597850Genetic Services Laboratory, University of Chicagocriteria provided, single submitter
Likely benign
(Mar 8, 2017)
germlineclinical testing

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

SCV000708998EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Benign
(Jun 7, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical 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 GeneDx, SCV000589445.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

A variant of uncertain significance has been identified in the VLDLR gene. The N81S variant has been reported previously in a study of macular degeneration; however additional information was not provided (Seddon et al., 2013). The N81S variant is observed in 118/16,512 (0.7%) alleles from individuals of South Asian background, including two homozygous individuals (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N81S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Asparagine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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

From Genetic Services Laboratory, University of Chicago, SCV000597850.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000708998.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Jul 10, 2021

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