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NM_024301.5(FKRP):c.469G>C (p.Ala157Pro) AND Autosomal recessive limb-girdle muscular dystrophy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 12, 2023
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:
RCV003324234.2

Allele description [Variation Report for NM_024301.5(FKRP):c.469G>C (p.Ala157Pro)]

NM_024301.5(FKRP):c.469G>C (p.Ala157Pro)

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.469G>C (p.Ala157Pro)
HGVS:
  • NC_000019.10:g.46755919G>C
  • NG_008898.2:g.14874G>C
  • NM_001039885.3:c.469G>C
  • NM_024301.4:c.469G>C
  • NM_024301.5:c.469G>CMANE SELECT
  • NP_001034974.1:p.Ala157Pro
  • NP_077277.1:p.Ala157Pro
  • LRG_761t1:c.469G>C
  • LRG_761:g.14874G>C
  • LRG_761p1:p.Ala157Pro
  • NC_000019.9:g.47259176G>C
  • NM_024301.5:c.469G>C
Protein change:
A157P
Links:
dbSNP: rs727502842
NCBI 1000 Genomes Browser:
rs727502842
Molecular consequence:
  • NM_001039885.3:c.469G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024301.5:c.469G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy
Identifiers:
MONDO: MONDO:0015152; MedGen: C2931907; OMIM: PS253600

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004029699Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Jul 12, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.

Sframeli M, Sarkozy A, Bertoli M, Astrea G, Hudson J, Scoto M, Mein R, Yau M, Phadke R, Feng L, Sewry C, Fen ANS, Longman C, McCullagh G, Straub V, Robb S, Manzur A, Bushby K, Muntoni F.

Neuromuscul Disord. 2017 Sep;27(9):793-803. doi: 10.1016/j.nmd.2017.06.008. Epub 2017 Jun 16.

PubMed [citation]
PMID:
28688748

Illness-associated muscle weakness in dystroglycanopathies.

Carlson CR, McGaughey SD, Eskuri JM, Stephan CM, Zimmerman MB, Mathews KD.

Neurology. 2017 Dec 5;89(23):2374-2380. doi: 10.1212/WNL.0000000000004720. Epub 2017 Nov 3.

PubMed [citation]
PMID:
29101272
PMCID:
PMC5719925
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004029699.1

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

Description

Variant summary: FKRP c.469G>C (p.Ala157Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 123906 control chromosomes (gnomAD). c.469G>C has been reported in the literature in individuals affected with Limb-Girdle Muscular Dystrophy or dystroglycanopathy (Sveen_2006, Sframeli_2017, Carlson_2017), including patients reported as compound heterozygous with a pathogenic variant. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16634037, 21970816, 28688748, 29101272). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Sep 29, 2024