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NM_001171.6(ABCC6):c.1255C>T (p.Arg419Trp) AND Autosomal recessive inherited pseudoxanthoma elasticum

Germline classification:
Likely pathogenic (1 submission)
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:
RCV002510593.2

Allele description [Variation Report for NM_001171.6(ABCC6):c.1255C>T (p.Arg419Trp)]

NM_001171.6(ABCC6):c.1255C>T (p.Arg419Trp)

Gene:
ABCC6:ATP binding cassette subfamily C member 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.11
Genomic location:
Preferred name:
NM_001171.6(ABCC6):c.1255C>T (p.Arg419Trp)
HGVS:
  • NC_000016.10:g.16198104G>A
  • NG_007558.3:g.30514C>T
  • NM_001171.6:c.1255C>TMANE SELECT
  • NM_001351800.1:c.913C>T
  • NP_001162.5:p.Arg419Trp
  • NP_001338729.1:p.Arg305Trp
  • LRG_1115t1:c.1255C>T
  • LRG_1115:g.30514C>T
  • LRG_1115p1:p.Arg419Trp
  • NC_000016.9:g.16291961G>A
  • NG_007558.2:g.30368C>T
  • NM_001171.5:c.1255C>T
  • NR_147784.1:n.1292C>T
Protein change:
R305W
Links:
dbSNP: rs775853778
NCBI 1000 Genomes Browser:
rs775853778
Molecular consequence:
  • NM_001171.6:c.1255C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351800.1:c.913C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_147784.1:n.1292C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Autosomal recessive inherited pseudoxanthoma elasticum (PXE)
Synonyms:
Gronblad Strandberg syndrome
Identifiers:
MONDO: MONDO:0009925; MedGen: C1275116; Orphanet: 758; OMIM: 264800

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002820239Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenicgermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV002820239.1

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

Description

The missense variant p.R419W in ABCC6 (NM_001171.6) has been reported in previously in compound heterozygous state in patients affected with Angioid Streaks (Katagiri et al, 2017). 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) indicates that this missense variant is expected to disrupt ABCC6 protein function. This variant disrupts the p.Arg419 amino acid residue in ABCC6. There is a moderate physicochemical difference between arginine and tryptophan. The p.Arg419Trp variant is novel (not in any individuals) in 1000 Genomes. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Arg419Trp in ABCC6 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024