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NM_001159699.2(FHL1):c.506G>A (p.Cys169Tyr) AND X-linked myopathy with postural muscle atrophy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 17, 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:
RCV003511981.2

Allele description [Variation Report for NM_001159699.2(FHL1):c.506G>A (p.Cys169Tyr)]

NM_001159699.2(FHL1):c.506G>A (p.Cys169Tyr)

Gene:
FHL1:four and a half LIM domains 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq26.3
Genomic location:
Preferred name:
NM_001159699.2(FHL1):c.506G>A (p.Cys169Tyr)
HGVS:
  • NC_000023.11:g.136207918G>A
  • NG_015895.1:g.65519G>A
  • NM_001159699.2:c.506G>AMANE SELECT
  • NM_001159700.2:c.458G>A
  • NM_001159701.2:c.545G>A
  • NM_001159702.3:c.458G>A
  • NM_001159703.2:c.458G>A
  • NM_001159704.1:c.458G>A
  • NM_001167819.1:c.458G>A
  • NM_001330659.2:c.506G>A
  • NM_001369326.1:c.458G>A
  • NM_001369327.2:c.458G>A
  • NM_001369328.1:c.458G>A
  • NM_001369329.1:c.458G>A
  • NM_001369330.1:c.458G>A
  • NM_001369331.1:c.458G>A
  • NM_001449.5:c.458G>A
  • NP_001153171.1:p.Cys169Tyr
  • NP_001153172.1:p.Cys153Tyr
  • NP_001153173.1:p.Cys182Tyr
  • NP_001153174.1:p.Cys153Tyr
  • NP_001153175.1:p.Cys153Tyr
  • NP_001153176.1:p.Cys153Tyr
  • NP_001161291.1:p.Cys153Tyr
  • NP_001317588.1:p.Cys169Tyr
  • NP_001356255.1:p.Cys153Tyr
  • NP_001356256.1:p.Cys153Tyr
  • NP_001356257.1:p.Cys153Tyr
  • NP_001356258.1:p.Cys153Tyr
  • NP_001356259.1:p.Cys153Tyr
  • NP_001356260.1:p.Cys153Tyr
  • NP_001440.2:p.Cys153Tyr
  • LRG_739t1:c.506G>A
  • LRG_739t2:c.458G>A
  • LRG_739:g.65519G>A
  • LRG_739p1:p.Cys169Tyr
  • LRG_739p2:p.Cys153Tyr
  • NC_000023.10:g.135290077G>A
  • NR_027621.2:n.869G>A
  • Q13642:p.Cys153Tyr
Protein change:
C153Y; CYS153TYR
Links:
UniProtKB: Q13642#VAR_046002; OMIM: 300163.0007; dbSNP: rs122458145
NCBI 1000 Genomes Browser:
rs122458145
Molecular consequence:
  • NM_001159699.2:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159700.2:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159701.2:c.545G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159702.3:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159703.2:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159704.1:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167819.1:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330659.2:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369326.1:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369327.2:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369328.1:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369329.1:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369330.1:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369331.1:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001449.5:c.458G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027621.2:n.869G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
X-linked myopathy with postural muscle atrophy
Identifiers:
MONDO: MONDO:0010401; MedGen: C2678055; OMIM: 300696

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004298993Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jul 17, 2023)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Targeted next-generation sequencing assay for detection of mutations in primary myopathies.

Evilä A, Arumilli M, Udd B, Hackman P.

Neuromuscul Disord. 2016 Jan;26(1):7-15. doi: 10.1016/j.nmd.2015.10.003. Epub 2015 Nov 25.

PubMed [citation]
PMID:
26627873

FHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation.

Wilding BR, McGrath MJ, Bonne G, Mitchell CA.

J Cell Sci. 2014 May 15;127(Pt 10):2269-81. doi: 10.1242/jcs.140905. Epub 2014 Mar 14.

PubMed [citation]
PMID:
24634512
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298993.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 153 of the FHL1 protein (p.Cys153Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with X-linked dominant FHL1-related conditions (PMID: 18274675, 26627873; Invitae). ClinVar contains an entry for this variant (Variation ID: 11553). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects FHL1 function (PMID: 24634512). This variant disrupts the p.Cys153 amino acid residue in FHL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18274675, 23965743). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024