NM_000384.3(APOB):c.2585T>C (p.Val862Ala) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Apr 16, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000468217.1

Allele description [Variation Report for NM_000384.3(APOB):c.2585T>C (p.Val862Ala)]

NM_000384.3(APOB):c.2585T>C (p.Val862Ala)

Gene:
APOB:apolipoprotein B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p24.1
Genomic location:
Preferred name:
NM_000384.3(APOB):c.2585T>C (p.Val862Ala)
HGVS:
  • NC_000002.12:g.21023544A>G
  • NG_011793.1:g.25530T>C
  • NM_000384.3:c.2585T>CMANE SELECT
  • NP_000375.3:p.Val862Ala
  • NC_000002.11:g.21246416A>G
  • NM_000384.2:c.2585T>C
Protein change:
V862A
Links:
dbSNP: rs145142090
NCBI 1000 Genomes Browser:
rs145142090
Molecular consequence:
  • NM_000384.3:c.2585T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hypercholesterolemia 2 (FHCL2)
Synonyms:
APOLIPOPROTEIN B-100, FAMILIAL DEFECTIVE; APOLIPOPROTEIN B-100, FAMILIAL LIGAND-DEFECTIVE; HYPERCHOLESTEROLEMIA, FAMILIAL, DUE TO LIGAND-DEFECTIVE APOLIPOPROTEIN B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007751; MedGen: C1704417; OMIM: 144010
Name:
Hypobetalipoproteinemia, familial, 1 (FHBL1)
Synonyms:
HYPOBETALIPOPROTEINEMIA, FAMILIAL
Identifiers:
MONDO: MONDO:0014252; MedGen: C4551990; OMIM: 615558

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000541937Invitaecriteria provided, single submitter
Uncertain significance
(Apr 16, 2016)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000541937.2

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

Description

This sequence change replaces valine with alanine at codon 862 of the APOB protein (p.Val862Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs145142090, ExAC <0.01%). This variant was reported in a family affected with premature myocardial infarction but it did not segregate with the disease (PMID: 26036859). ClinVar contains an entry for this variant (Variation ID: 189305). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jun 2, 2021

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