NM_001114753.3(ENG):c.321_322delinsTT (p.His108Tyr) AND Hereditary hemorrhagic telangiectasia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 14, 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:: RCV000473361.12

Allele description [Variation Report for NM_001114753.3(ENG):c.321_322delinsTT (p.His108Tyr)]

NM_001114753.3(ENG):c.321_322delinsTT (p.His108Tyr)

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.321_322delinsTT (p.His108Tyr)

HGVS:

NC_000009.12:g.127829725_127829726delinsAA
NG_009551.1:g.30043_30044delinsTT
NM_000118.4:c.321_322delGCinsTT
NM_001114753.3:c.321_322delinsTTMANE SELECT
NM_001278138.2:c.-226_-225delinsTT
NM_001406715.1:c.321_322delGCinsTT
NP_000109.1:p.His108Tyr
NP_000109.1:p.His108Tyr
NP_001108225.1:p.His108Tyr
NP_001108225.1:p.His108Tyr
NP_001393644.1:p.His108Tyr
LRG_589t1:c.321_322delinsTT
LRG_589t2:c.321_322delinsTT
LRG_589:g.30043_30044delinsTT
LRG_589p1:p.His108Tyr
NC_000009.11:g.130592004_130592005delinsAA
NM_000118.3:c.321_322delGCinsTT
NM_000118.3:c.321_322delinsTT
NM_001114753.1:c.321_322delGCinsTT
NM_001114753.1:c.321_322delinsTT
NM_001114753.2:c.321_322delGCinsTT
NM_001114753.2:c.321_322delinsTT

Protein change:

H108Y

Links:

dbSNP: rs1060501425

NCBI 1000 Genomes Browser:

rs1060501425

Molecular consequence:

NM_001278138.2:c.-226_-225delinsTT - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000118.4:c.321_322delGCinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001114753.3:c.321_322delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001406715.1:c.321_322delGCinsTT - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000546134	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25312062, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000546134

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 14, 2023)

germline

clinical testing

PubMed (2)
[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

Functional analysis of endoglin mutations from hereditary hemorrhagic telangiectasia type 1 patients reveals different mechanisms for endoglin loss of function.

Mallet C, Lamribet K, Giraud S, Dupuis-Girod S, Feige JJ, Bailly S, Tillet E.

Hum Mol Genet. 2015 Feb 15;24(4):1142-54. doi: 10.1093/hmg/ddu531. Epub 2014 Oct 13.

PubMed [citation]

PMID:: 25312062

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000546134.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 108 of the ENG protein (p.His108Tyr). 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: 25312062). ClinVar contains an entry for this variant (Variation ID: 407139). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change does not substantially affect ENG function (PMID: 25312062). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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