NM_000118.3(ENG):c.1080_1083del (p.Thr361fs) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jun 24, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000200429.4

Allele description [Variation Report for NM_000118.3(ENG):c.1080_1083del (p.Thr361fs)]

NM_000118.3(ENG):c.1080_1083del (p.Thr361fs)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.1080_1083del (p.Thr361fs)
HGVS:
  • NC_000009.12:g.127824357_127824360del
  • NG_009551.1:g.35411_35414del
  • NM_000118.3:c.1080_1083del
  • NM_001114753.2:c.1080_1083del
  • NM_001278138.1:c.534_537del
  • NP_000109.1:p.Thr361fs
  • NP_001108225.1:p.Thr361fs
  • NP_001265067.1:p.Thr179fs
  • LRG_589t1:c.1080_1083del
  • LRG_589t2:c.1080_1083del
  • LRG_589:g.35411_35414del
  • LRG_589p1:p.Thr361fs
  • LRG_589p2:p.Thr361fs
  • NC_000009.11:g.130586636_130586639del
  • NM_000118.2:c.1080_1083delGACA
  • NM_000118.3:c.1080_1083delGACA
  • NM_001114753.2:c.1080_1083delGACA
  • p.T361Sfs*7
  • p.Thr361Serfs*7
Protein change:
T179fs
Links:
dbSNP: rs863223540
NCBI 1000 Genomes Browser:
rs863223540
Molecular consequence:
  • NM_000118.3:c.1080_1083del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001114753.2:c.1080_1083del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001278138.1:c.534_537del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000250087GeneDxcriteria provided, single submitter
Pathogenic
(Jul 24, 2018)
germlineclinical testing

Citation Link,

SCV001713507Mayo Clinic Laboratories, Mayo Cliniccriteria provided, single submitter
Pathogenic
(Jun 24, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.

Gallione CJ, Klaus DJ, Yeh EY, Stenzel TT, Xue Y, Anthony KB, McAllister KA, Baldwin MA, Berg JN, Lux A, Smith JD, Vary CP, Craigen WJ, Westermann CJ, Warner ML, Miller YE, Jackson CE, Guttmacher AE, Marchuk DA.

Hum Mutat. 1998;11(4):286-94.

PubMed [citation]
PMID:
9554745

Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations.

Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M.

Hum Mutat. 2005 Mar;25(3):320.

PubMed [citation]
PMID:
15712270
See all PubMed Citations (8)

Details of each submission

From GeneDx, SCV000250087.12

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

Description

The c.1080_1083delGACA pathogenic variant in the ENG gene, also reported as c.1078_1081delGACA due to alternate nomenclature, has been identified previously in multiple members of a large family with HHT (Gallione et al., 1998). It has also been identified in several other unrelated individuals with HHT (Wehner et al., 2006; Bossler wt al., 2006; Olivieri et al., 2007; Nishida et al., 2012). Additionally, the c.1080_1083delGACA variant has not been observed in large population cohorts (Lek et al., 2016). The c.1080_1083delGACA variant causes a shift in reading frame starting at codon threonine 361, changing it to a serine, and creating a premature stop codon at position 7 of the new reading frame, denoted p.Thr361SerfsX7. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Furthermore, other frameshift variants in the ENG gene have been reported in Human Gene Mutation Database in association with HHT (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713507.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (8)

Description

PVS1, PS4, PP1_Strong, PM2, PP4

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Jun 14, 2021

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