NM_000118.3(ENG):c.1702G>A (p.Val568Ile) AND Hereditary hemorrhagic telangiectasia type 1

Clinical significance:Uncertain significance (Last evaluated: Jun 28, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000468455.1

Allele description [Variation Report for NM_000118.3(ENG):c.1702G>A (p.Val568Ile)]

NM_000118.3(ENG):c.1702G>A (p.Val568Ile)

Genes:
ENG:endoglin [Gene - OMIM - HGNC]
LOC102723566:uncharacterized LOC102723566 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.1702G>A (p.Val568Ile)
HGVS:
  • NC_000009.12:g.127817188C>T
  • NG_009551.1:g.42581G>A
  • NM_000118.3:c.1702G>A
  • NM_001114753.2:c.1702G>A
  • NM_001278138.1:c.1156G>A
  • NP_000109.1:p.Val568Ile
  • NP_001108225.1:p.Val568Ile
  • NP_001265067.1:p.Val386Ile
  • LRG_589t1:c.1702G>A
  • LRG_589t2:c.1702G>A
  • LRG_589:g.42581G>A
  • LRG_589p1:p.Val568Ile
  • LRG_589p2:p.Val568Ile
  • NC_000009.11:g.130579467C>T
  • NR_136302.1:n.1123C>T
Protein change:
V386I
Links:
dbSNP: rs781201877
NCBI 1000 Genomes Browser:
rs781201877
Molecular consequence:
  • NM_000118.3:c.1702G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.2:c.1702G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.1:c.1156G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136302.1:n.1123C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary hemorrhagic telangiectasia type 1 (HHT1)
Synonyms:
Osler Weber Rendu syndrome type 1
Identifiers:
MONDO: MONDO:0008535; MedGen: C4551861; Orphanet: 774; OMIM: 187300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000546119Invitaecriteria provided, single submitter
Uncertain significance
(Jun 28, 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, SCV000546119.2

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

Description

This sequence change replaces valine with isoleucine at codon 568 of the ENG protein (p.Val568Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs781201877, ExAC <0.01%) but has not been reported in the literature in individuals with a ENG-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The isoleucine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect 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: Apr 12, 2021

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