NM_000118.3(ENG):c.41T>C (p.Leu14Pro) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Likely pathogenic (Last evaluated: Jan 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001377784.1

Allele description [Variation Report for NM_000118.3(ENG):c.41T>C (p.Leu14Pro)]

NM_000118.3(ENG):c.41T>C (p.Leu14Pro)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.41T>C (p.Leu14Pro)
HGVS:
  • NC_000009.12:g.127854315A>G
  • NG_009551.1:g.5454T>C
  • NM_000118.3:c.41T>C
  • NM_001114753.2:c.41T>C
  • NP_000109.1:p.Leu14Pro
  • NP_001108225.1:p.Leu14Pro
  • LRG_589t1:c.41T>C
  • LRG_589t2:c.41T>C
  • LRG_589:g.5454T>C
  • LRG_589p1:p.Leu14Pro
  • LRG_589p2:p.Leu14Pro
  • NC_000009.11:g.130616594A>G
Protein change:
L14P
Links:
dbSNP: rs1554813788
NCBI 1000 Genomes Browser:
rs1554813788
Molecular consequence:
  • NM_000118.3:c.41T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.2:c.41T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary hemorrhagic telangiectasia (HHT)
Synonyms:
Osler Weber Rendu syndrome; ORW disease; Osler-Rendu-Weber disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019180; MedGen: C0039445; OMIM: PS187300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001575207Invitaecriteria provided, single submitter
Likely pathogenic
(Jan 11, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis.

McDonald J, Damjanovich K, Millson A, Wooderchak W, Chibuk JM, Stevenson DA, Gedge F, Bayrak-Toydemir P.

Clin Genet. 2011 Apr;79(4):335-44. doi: 10.1111/j.1399-0004.2010.01596.x. Epub 2010 Dec 16.

PubMed [citation]
PMID:
21158752

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, SCV001575207.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces leucine with proline at codon 14 of the ENG protein (p.Leu14Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (PMID: 21158752, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 439647). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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