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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Homo sapiens PAPPA antisense RNA 1 (PAPPA-AS1), long non-coding RNA
Homo sapiens PAPPA antisense RNA 1 (PAPPA-AS1), long non-coding RNA
gi|512125254|ref|NR_103711.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003441310	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 24, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15517393, 17384219, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003441310

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 24, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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