NM_000020.2(ACVRL1):c.1231C>T (p.Arg411Trp) AND not provided

Clinical significance:Pathogenic (Last evaluated: Nov 15, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000199381.2

Allele description [Variation Report for NM_000020.2(ACVRL1):c.1231C>T (p.Arg411Trp)]

NM_000020.2(ACVRL1):c.1231C>T (p.Arg411Trp)

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_000020.2(ACVRL1):c.1231C>T (p.Arg411Trp)
Other names:
p.R411W:CGG>TGG
HGVS:
  • NC_000012.12:g.51916218C>T
  • NG_009549.1:g.13801C>T
  • NM_000020.2:c.1231C>T
  • NM_001077401.2:c.1231C>T
  • NP_000011.2:p.Arg411Trp
  • NP_001070869.1:p.Arg411Trp
  • LRG_543t1:c.1231C>T
  • LRG_543:g.13801C>T
  • LRG_543p1:p.Arg411Trp
  • NC_000012.11:g.52310002C>T
  • P37023:p.Arg411Trp
Protein change:
R411W; ARG411TRP
Links:
UniProtKB: P37023#VAR_026809; OMIM: 601284.0009; dbSNP: rs121909287
NCBI 1000 Genomes Browser:
rs121909287
Molecular consequence:
  • NM_000020.2:c.1231C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.1231C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000249635GeneDxcriteria provided, single submitter
Pathogenic
(Nov 15, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000249635.11

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

Description

The R411W pathogenic variant in the ACVRL1 gene has been reported in association with HHT and PAH (Trembath et al., 2001; Abdalla et al., 2003; Lesca et al., 2004; Letteboer et al., 2005; Schulte et al., 2005). R411W is not observed in large population cohorts (Lek et al., 2016). The R411W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Furthermore, functional studies show that R411W results in defective BMP9 response and impaired ALK1 activity due to abnormal ALK1 trafficking (Ricard et al., 2010; Hume et al., 2013). Lastly, missense variants at the same and nearby residues (R411Q, E407G) have been reported in the Human Gene Mutation Database in association with HHT (Stenson et al., 2014), supporting the functional importance of this region of the protein.

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

Last Updated: May 10, 2021

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