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NM_001114753.3(ENG):c.1121_1122delinsGC (p.Lys374Ser) AND Hereditary hemorrhagic telangiectasia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 24, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003096217.4

Allele description [Variation Report for NM_001114753.3(ENG):c.1121_1122delinsGC (p.Lys374Ser)]

NM_001114753.3(ENG):c.1121_1122delinsGC (p.Lys374Ser)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.1121_1122delinsGC (p.Lys374Ser)
HGVS:
  • NC_000009.12:g.127824316_127824317delinsGC
  • NG_009551.1:g.35452_35453delinsGC
  • NM_000118.4:c.1121_1122delAAinsGC
  • NM_001114753.3:c.1121_1122delinsGCMANE SELECT
  • NM_001278138.2:c.575_576delinsGC
  • NM_001406715.1:c.1121_1122delAAinsGC
  • NP_000109.1:p.Lys374Ser
  • NP_000109.1:p.Lys374Ser
  • NP_001108225.1:p.Lys374Ser
  • NP_001108225.1:p.Lys374Ser
  • NP_001265067.1:p.Lys192Ser
  • NP_001393644.1:p.Lys374Ser
  • LRG_589t1:c.1121_1122delinsGC
  • LRG_589t2:c.1121_1122delAAinsGC
  • LRG_589:g.35452_35453delinsGC
  • LRG_589p1:p.Lys374Ser
  • LRG_589p2:p.Lys374Ser
  • NC_000009.11:g.130586595_130586596delinsGC
  • NM_000118.3:c.1121_1122delinsGC
  • NM_001114753.1:c.1121_1122delAAinsGC
  • NM_001114753.2:c.1121_1122delAAinsGC
Protein change:
K192S
Links:
dbSNP: rs2131885751
NCBI 1000 Genomes Browser:
rs2131885751
Molecular consequence:
  • NM_000118.4:c.1121_1122delAAinsGC - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.1121_1122delinsGC - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.575_576delinsGC - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406715.1:c.1121_1122delAAinsGC - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003441310Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 24, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients.

Letteboer TG, Zewald RA, Kamping EJ, de Haas G, Mager JJ, Snijder RJ, Lindhout D, Hennekam FA, Westermann CJ, Ploos van Amstel JK.

Hum Genet. 2005 Jan;116(1-2):8-16. Epub 2004 Oct 23.

PubMed [citation]
PMID:
15517393

Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations.

Gedge F, McDonald J, Phansalkar A, Chou LS, Calderon F, Mao R, Lyon E, Bayrak-Toydemir P.

J Mol Diagn. 2007 Apr;9(2):258-65.

PubMed [citation]
PMID:
17384219
PMCID:
PMC1867450
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003441310.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces lysine, which is basic and polar, with serine, which is neutral and polar, at codon 374 of the ENG protein (p.Lys374Ser). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 15517393, 17384219; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1701581). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 20, 2024