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:: RCV003511981.4

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

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
Synonyms:: FHL1-Related Emery-Dreifuss Muscular Dystrophy, X-Linked
Identifiers:: MONDO: MONDO:0010401; MedGen: C2678055; OMIM: 300696

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298993	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23965743, 24634512, 18274675, 26627873, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298993

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 17, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related disorders.

Malfatti E, Olivé M, Taratuto AL, Richard P, Brochier G, Bitoun M, Gueneau L, Laforêt P, Stojkovic T, Maisonobe T, Monges S, Lubieniecki F, Vasquez G, Streichenberger N, Lacène E, Saccoliti M, Prudhon B, Alexianu M, Figarella-Branger D, Schessl J, Bonnemann C, Eymard B, et al.

J Neuropathol Exp Neurol. 2013 Sep;72(9):833-45. doi: 10.1097/NEN.0b013e3182a23506.

PubMed [citation]

PMID:: 23965743
PMCID:: PMC5210222

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, SCV004298993.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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). 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. 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. Experimental studies have shown that this missense change affects FHL1 function (PMID: 24634512). 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. ClinVar contains an entry for this variant (Variation ID: 11553). This missense change has been observed in individuals with X-linked dominant FHL1-related conditions (PMID: 18274675, 26627873; Invitae).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

ClinVar

Relating variation to medicine