NM_000020.3(ACVRL1):c.938T>G (p.Leu313Arg) AND Telangiectasia, hereditary hemorrhagic, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 5, 2022
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:: RCV002937639.3

Allele description [Variation Report for NM_000020.3(ACVRL1):c.938T>G (p.Leu313Arg)]

NM_000020.3(ACVRL1):c.938T>G (p.Leu313Arg)

Gene:

ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000020.3(ACVRL1):c.938T>G (p.Leu313Arg)

HGVS:

NC_000012.12:g.51915390T>G
NG_009549.1:g.12973T>G
NG_125718.1:g.689T>G
NM_000020.3:c.938T>GMANE SELECT
NM_001077401.2:c.938T>G
NM_001406487.1:c.938T>G
NM_001406488.1:c.938T>G
NM_001406489.1:c.938T>G
NM_001406490.1:c.626T>G
NM_001406491.1:c.626T>G
NM_001406492.1:c.626T>G
NM_001406493.1:c.626T>G
NM_001406494.1:c.626T>G
NM_001406495.1:c.374T>G
NP_000011.2:p.Leu313Arg
NP_000011.2:p.Leu313Arg
NP_001070869.1:p.Leu313Arg
NP_001393416.1:p.Leu313Arg
NP_001393417.1:p.Leu313Arg
NP_001393418.1:p.Leu313Arg
NP_001393419.1:p.Leu209Arg
NP_001393420.1:p.Leu209Arg
NP_001393421.1:p.Leu209Arg
NP_001393422.1:p.Leu209Arg
NP_001393423.1:p.Leu209Arg
NP_001393424.1:p.Leu125Arg
LRG_543t1:c.938T>G
LRG_543:g.12973T>G
LRG_543p1:p.Leu313Arg
NC_000012.11:g.52309174T>G
NM_000020.2:c.938T>G

Protein change:

L125R

Molecular consequence:

NM_000020.3:c.938T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077401.2:c.938T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406487.1:c.938T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406488.1:c.938T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406489.1:c.938T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406490.1:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406491.1:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406492.1:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406493.1:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406494.1:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406495.1:c.374T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Telangiectasia, hereditary hemorrhagic, type 2 (HHT2)
Synonyms:: Telangiectasia, hereditary hemorrhagic, type II; Osler Weber Rendu syndrome type 2
Identifiers:: MONDO: MONDO:0010880; MedGen: C1838163; Orphanet: 774; OMIM: 600376

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003260495	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 5, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23535011, 26176610, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003260495

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 5, 2022)

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: arteriovenous malformations in children.

Giordano P, Lenato GM, Suppressa P, Lastella P, Dicuonzo F, Chiumarulo L, Sangerardi M, Piccarreta P, Valerio R, Scardapane A, Marano G, Resta N, Quaranta N, Sabbà C.

J Pediatr. 2013 Jul;163(1):179-86.e1-3. doi: 10.1016/j.jpeds.2013.02.009. Epub 2013 Mar 25.

PubMed [citation]

PMID:: 23535011

Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by Hereditary Hemorrhagic Telangiectasia.

Alaa El Din F, Patri S, Thoreau V, Rodriguez-Ballesteros M, Hamade E, Bailly S, Gilbert-Dussardier B, Abou Merhi R, Kitzis A.

PLoS One. 2015;10(7):e0132111. doi: 10.1371/journal.pone.0132111.

PubMed [citation]

PMID:: 26176610
PMCID:: PMC4503601

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003260495.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACVRL1 protein function. This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 313 of the ACVRL1 protein (p.Leu313Arg). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu313 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 23535011, 26176610), which suggests that this may be a clinically significant amino acid residue.

#	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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