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NM_024301.5(FKRP):c.928G>T (p.Glu310Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 29, 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:
RCV002369793.2

Allele description [Variation Report for NM_024301.5(FKRP):c.928G>T (p.Glu310Ter)]

NM_024301.5(FKRP):c.928G>T (p.Glu310Ter)

Gene:
FKRP:fukutin related protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.32
Genomic location:
Preferred name:
NM_024301.5(FKRP):c.928G>T (p.Glu310Ter)
HGVS:
  • NC_000019.10:g.46756378G>T
  • NG_008898.2:g.15333G>T
  • NM_001039885.3:c.928G>T
  • NM_024301.5:c.928G>TMANE SELECT
  • NP_001034974.1:p.Glu310Ter
  • NP_077277.1:p.Glu310Ter
  • LRG_761t1:c.928G>T
  • LRG_761:g.15333G>T
  • LRG_761p1:p.Glu310Ter
  • NC_000019.9:g.47259635G>T
  • NM_024301.4:c.928G>T
Protein change:
E310*
Links:
dbSNP: rs765885747
NCBI 1000 Genomes Browser:
rs765885747
Molecular consequence:
  • NM_001039885.3:c.928G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_024301.5:c.928G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002686875Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Apr 29, 2022) 		germlineclinical testing

PubMed (6)
[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

The phenotype of limb-girdle muscular dystrophy type 2I.

Poppe M, Cree L, Bourke J, Eagle M, Anderson LV, Birchall D, Brockington M, Buddles M, Busby M, Muntoni F, Wills A, Bushby K.

Neurology. 2003 Apr 22;60(8):1246-51.

PubMed [citation]
PMID:
12707425

The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations.

Frosk P, Greenberg CR, Tennese AA, Lamont R, Nylen E, Hirst C, Frappier D, Roslin NM, Zaik M, Bushby K, Straub V, Zatz M, de Paula F, Morgan K, Fujiwara TM, Wrogemann K.

Hum Mutat. 2005 Jan;25(1):38-44.

PubMed [citation]
PMID:
15580560
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002686875.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The p.E310* variant (also known as c.928G>T), located in coding exon 1 of the FKRP gene, results from a G to T substitution at nucleotide position 928. This changes the amino acid from a glutamic acid to a stop codon within coding exon 1. This alteration occurs at the 3' terminus of theFKRP gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 186 (38%) 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 in compound heterozygotes from limb-girdle muscular dystrophy cohorts (Poppe M et al. Neurology, 2003 Apr;60:1246-51; Frosk P et al. Hum Mutat, 2005 Jan;25:38-44; Murphy LB et al. Ann Clin Transl Neurol, 2020 05;7:757-766). Other truncating alterations downstream have been observed in individuals with a personal and/or family history that is consistent with FKRP-related disease (Mercuri E et al. Arch. Neurol., 2006 Feb;63:251-7; 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