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NM_024301.5(FKRP):c.899T>C (p.Val300Ala) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 13, 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:
RCV002371759.3

Allele description [Variation Report for NM_024301.5(FKRP):c.899T>C (p.Val300Ala)]

NM_024301.5(FKRP):c.899T>C (p.Val300Ala)

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.899T>C (p.Val300Ala)
HGVS:
  • NC_000019.10:g.46756349T>C
  • NG_008898.2:g.15304T>C
  • NM_001039885.3:c.899T>C
  • NM_024301.5:c.899T>CMANE SELECT
  • NP_001034974.1:p.Val300Ala
  • NP_077277.1:p.Val300Ala
  • LRG_761t1:c.899T>C
  • LRG_761:g.15304T>C
  • LRG_761p1:p.Val300Ala
  • NC_000019.9:g.47259606T>C
  • NM_024301.4:c.899T>C
  • Q9H9S5:p.Val300Ala
Protein change:
V300A; VAL300ALA
Links:
UniProtKB: Q9H9S5#VAR_065060; OMIM: 606596.0015; dbSNP: rs104894691
NCBI 1000 Genomes Browser:
rs104894691
Molecular consequence:
  • NM_001039885.3:c.899T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024301.5:c.899T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002683737Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 13, 2022) 		germlineclinical testing

PubMed (4)
[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

Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.

de Paula F, Vieira N, Starling A, Yamamoto LU, Lima B, de Cássia Pavanello R, Vainzof M, Nigro V, Zatz M.

Eur J Hum Genet. 2003 Dec;11(12):923-30.

PubMed [citation]
PMID:
14647208

FKRP (826C>A) frequently causes limb-girdle muscular dystrophy in German patients.

Walter MC, Petersen JA, Stucka R, Fischer D, Schröder R, Vorgerd M, Schroers A, Schreiber H, Hanemann CO, Knirsch U, Rosenbohm A, Huebner A, Barisic N, Horvath R, Komoly S, Reilich P, Müller-Felber W, Pongratz D, Müller JS, Auerswald EA, Lochmüller H.

J Med Genet. 2004 Apr;41(4):e50. No abstract available.

PubMed [citation]
PMID:
15060126
PMCID:
PMC1735747
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002683737.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The p.V300A pathogenic mutation (also known as c.899T>C), located in coding exon 1 of the FKRP gene, results from a T to C substitution at nucleotide position 899. The valine at codon 300 is replaced by alanine, an amino acid with similar properties. This alteration has been reported in individuals with limb-girdle muscular dystrophy (LGMD), as either homozygous or compound heterozygous with an additional known pathogenic mutation in FKRP (de Paula F et al. Eur J Hum Genet, 2003 Dec;11:923-30; Walter MC et al. J Med Genet, 2004 Apr;41:e50; Stensland E et al. Neuromuscul Disord, 2011 Jan;21:41-6). Additionally, an in vitro assay showed this alteration may impact protein function (Henriques SF et al. Hum Mutat, 2019 10;40:1874-1885). Another alteration at the same codon, p.V300M (c.898G>A), has been detected in the homozygous and compound heterozygous states with pathogenic variants in individuals reported to have LGMD or clinical suspicion of LGMD (de Paula F et al. Eur. J. Hum. Genet., 2003 Dec;11:923-30; Frosk P et al. Hum. Mutat., 2005 Jan;25:38-44; Nallamilli BRR et al. Ann Clin Transl Neurol, 2018 Dec;5:1574-1587; Invitae pers. comm.). 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: May 12, 2024