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NM_024301.5(FKRP):c.1187dup (p.Ala397fs) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 14, 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:
RCV002334830.2

Allele description [Variation Report for NM_024301.5(FKRP):c.1187dup (p.Ala397fs)]

NM_024301.5(FKRP):c.1187dup (p.Ala397fs)

Gene:
FKRP:fukutin related protein [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
19q13.32
Genomic location:
Preferred name:
NM_024301.5(FKRP):c.1187dup (p.Ala397fs)
HGVS:
  • NC_000019.10:g.46756637dup
  • NG_008898.2:g.15592dup
  • NM_001039885.3:c.1187dup
  • NM_024301.5:c.1187dupMANE SELECT
  • NP_001034974.1:p.Ala397fs
  • NP_077277.1:p.Ala397fs
  • LRG_761t1:c.1187dup
  • LRG_761:g.15592dup
  • LRG_761p1:p.Ala397fs
  • NC_000019.9:g.47259892_47259893insA
  • NC_000019.9:g.47259894dup
  • NM_024301.4:c.1187dupA
Protein change:
A397fs
Links:
dbSNP: rs772020161
NCBI 1000 Genomes Browser:
rs772020161
Molecular consequence:
  • NM_001039885.3:c.1187dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_024301.5:c.1187dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002638721Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 14, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

LGMD2I presenting with a characteristic Duchenne or Becker muscular dystrophy phenotype.

Schwartz M, Hertz JM, Sveen ML, Vissing J.

Neurology. 2005 May 10;64(9):1635-7.

PubMed [citation]
PMID:
15883334

High prevalence and phenotype-genotype correlations of limb girdle muscular dystrophy type 2I in Denmark.

Sveen ML, Schwartz M, Vissing J.

Ann Neurol. 2006 May;59(5):808-15.

PubMed [citation]
PMID:
16634037
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002638721.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The c.1187dupA pathogenic mutation, located in coding exon 1 of the FKRP gene, results from a duplication of A at nucleotide position 1187, causing a translational frameshift with a predicted alternate stop codon (p.A397Gfs*67). This alteration occurs at the 3' terminus of theFKRP gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 20% (99 amino acids) of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant has been reported to co-occur with another pathogenic mutation in the FKRP gene in individuals reported to have limb-girdle muscular dystrophy (Sveen ML et al. Ann Neurol, 2006 May;59:808-15). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024