NM_024301.5(FKRP):c.235G>A (p.Val79Met) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Benign(1);Likely benign(1);Uncertain significance(1) (Last evaluated: Oct 23, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000236146.8

Allele description [Variation Report for NM_024301.5(FKRP):c.235G>A (p.Val79Met)]

NM_024301.5(FKRP):c.235G>A (p.Val79Met)

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.235G>A (p.Val79Met)
HGVS:
  • NC_000019.10:g.46755685G>A
  • NG_008898.2:g.14640G>A
  • NM_001039885.3:c.235G>A
  • NM_024301.5:c.235G>AMANE SELECT
  • NP_001034974.1:p.Val79Met
  • NP_077277.1:p.Val79Met
  • LRG_761t1:c.235G>A
  • LRG_761:g.14640G>A
  • LRG_761p1:p.Val79Met
  • NC_000019.9:g.47258942G>A
  • NM_024301.4:c.235G>A
  • Q9H9S5:p.Val79Met
Protein change:
V79M; VAL79MET
Links:
UniProtKB: Q9H9S5#VAR_065055; OMIM: 606596.0012; dbSNP: rs104894683
NCBI 1000 Genomes Browser:
rs104894683
Molecular consequence:
  • NM_001039885.3:c.235G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024301.5:c.235G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000230415EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Benign
(Apr 12, 2017)
germlineclinical testing

Citation Link,

SCV000594778Genetic Services Laboratory, University of Chicagocriteria provided, single submitter
Likely benign
(Dec 31, 2015)
germlineclinical testing

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

SCV001157673ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Oct 23, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot providednot providednot providedclinical testing
not providedgermlinenonot 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 EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000230415.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From Genetic Services Laboratory, University of Chicago, SCV000594778.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001157673.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The FKRP c.235G>A; p.Val79Met variant (rs104894683) is reported in several individuals affected with limb girdle muscular dystrophy (de Paula 2003), including three siblings that carried the p.Val79Met variant in trans to a nonsense variant (Vieira 2006). Of the three siblings, two were severely affected and also carried a p.Pro89Ala variant, which was not identified in the third mildly affected sibling (Vieira 2006). The p.Val79Met variant is reported in ClinVar (Variation ID: 4229) and is found in the African population with an overall allele frequency of 1.5% (320/21382 alleles, including one homozygote) in the Genome Aggregation Database. The valine at codon 79 is moderately conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to conflicting information, the clinical significance of the p.Val79Met variant is uncertain at this time. References: de Paula F et al. Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum. Eur J Hum Genet. 2003 Dec;11(12):923-30. Vieira NM et al. Mutation analysis in the FKRP gene provides an explanation for a rare cause of intrafamilial clinical variability in LGMD2I. Neuromuscul Disord. 2006 Dec;16(12):870-3.

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

Last Updated: Oct 2, 2021

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