NM_001159699.2(FHL1):c.507C>G (p.Cys169Trp) AND X-linked myopathy with postural muscle atrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 2, 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:: RCV003513700.3

Allele description [Variation Report for NM_001159699.2(FHL1):c.507C>G (p.Cys169Trp)]

NM_001159699.2(FHL1):c.507C>G (p.Cys169Trp)

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.507C>G (p.Cys169Trp)

HGVS:

NC_000023.11:g.136207919C>G
NG_015895.1:g.65520C>G
NM_001159699.2:c.507C>GMANE SELECT
NM_001159700.2:c.459C>G
NM_001159701.2:c.546C>G
NM_001159702.3:c.459C>G
NM_001159703.2:c.459C>G
NM_001159704.1:c.459C>G
NM_001167819.1:c.459C>G
NM_001330659.2:c.507C>G
NM_001369326.1:c.459C>G
NM_001369327.2:c.459C>G
NM_001369328.1:c.459C>G
NM_001369329.1:c.459C>G
NM_001369330.1:c.459C>G
NM_001369331.1:c.459C>G
NM_001449.5:c.459C>G
NP_001153171.1:p.Cys169Trp
NP_001153172.1:p.Cys153Trp
NP_001153173.1:p.Cys182Trp
NP_001153174.1:p.Cys153Trp
NP_001153175.1:p.Cys153Trp
NP_001153176.1:p.Cys153Trp
NP_001161291.1:p.Cys153Trp
NP_001317588.1:p.Cys169Trp
NP_001356255.1:p.Cys153Trp
NP_001356256.1:p.Cys153Trp
NP_001356257.1:p.Cys153Trp
NP_001356258.1:p.Cys153Trp
NP_001356259.1:p.Cys153Trp
NP_001356260.1:p.Cys153Trp
NP_001440.2:p.Cys153Trp
LRG_739t1:c.507C>G
LRG_739t2:c.459C>G
LRG_739:g.65520C>G
LRG_739p1:p.Cys169Trp
LRG_739p2:p.Cys153Trp
NC_000023.10:g.135290078C>G
NR_027621.2:n.870C>G

Protein change:

C153W

Links:

dbSNP: rs752839497

NCBI 1000 Genomes Browser:

rs752839497

Molecular consequence:

NM_001159699.2:c.507C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159700.2:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159701.2:c.546C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159702.3:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159703.2:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159704.1:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167819.1:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330659.2:c.507C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369326.1:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369327.2:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369328.1:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369329.1:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369330.1:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369331.1:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001449.5:c.459C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_027621.2:n.870C>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298994	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 2, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18274675, 23965743, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298994

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 2, 2023)

germline

clinical testing

PubMed (3)
[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

Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.

Schessl J, Zou Y, McGrath MJ, Cowling BS, Maiti B, Chin SS, Sewry C, Battini R, Hu Y, Cottle DL, Rosenblatt M, Spruce L, Ganguly A, Kirschner J, Judkins AR, Golden JA, Goebel HH, Muntoni F, Flanigan KM, Mitchell CA, Bönnemann CG.

J Clin Invest. 2008 Mar;118(3):904-12. doi: 10.1172/JCI34450.

PubMed [citation]

PMID:: 18274675
PMCID:: PMC2242623

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298994.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 153 of the FHL1 protein (p.Cys153Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of FHL1-related conditions (PMID: 23965743; Invitae). In at least one individual the variant was observed to be de novo. 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. 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. For these reasons, this variant has been classified as Pathogenic.

#	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: May 16, 2025

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