NM_001159699.2(FHL1):c.380-2A>G AND X-linked myopathy with postural muscle atrophy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 3, 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:: RCV002042415.8

Allele description [Variation Report for NM_001159699.2(FHL1):c.380-2A>G]

NM_001159699.2(FHL1):c.380-2A>G

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.380-2A>G

HGVS:

NC_000023.11:g.136207790A>G
NG_015895.1:g.65391A>G
NM_001159699.2:c.380-2A>GMANE SELECT
NM_001159700.2:c.332-2A>G
NM_001159701.2:c.419-2A>G
NM_001159702.3:c.332-2A>G
NM_001159703.2:c.332-2A>G
NM_001159704.1:c.332-2A>G
NM_001167819.1:c.332-2A>G
NM_001330659.2:c.380-2A>G
NM_001369326.1:c.332-2A>G
NM_001369327.2:c.332-2A>G
NM_001369328.1:c.332-2A>G
NM_001369329.1:c.332-2A>G
NM_001369330.1:c.332-2A>G
NM_001369331.1:c.332-2A>G
NM_001449.5:c.332-2A>G
LRG_739t1:c.380-2A>G
LRG_739t2:c.332-2A>G
LRG_739:g.65391A>G
NC_000023.10:g.135289949A>G

Links:

dbSNP: rs2148375467

Molecular consequence:

NM_001159699.2:c.380-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001159700.2:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001159701.2:c.419-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001159702.3:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001159703.2:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001159704.1:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001167819.1:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001330659.2:c.380-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369326.1:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369327.2:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369328.1:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369329.1:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369330.1:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369331.1:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001449.5:c.332-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002295362	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 3, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16199547, 18179888, 19687455, 19716112, 22523091, 24114807, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002295362

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 3, 2023)

germline

clinical testing

PubMed (7)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.

Windpassinger C, Schoser B, Straub V, Hochmeister S, Noor A, Lohberger B, Farra N, Petek E, Schwarzbraun T, Ofner L, Löscher WN, Wagner K, Lochmüller H, Vincent JB, Quasthoff S.

Am J Hum Genet. 2008 Jan;82(1):88-99. doi: 10.1016/j.ajhg.2007.09.004.

PubMed [citation]

PMID:: 18179888
PMCID:: PMC2253986

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002295362.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

ClinVar contains an entry for this variant (Variation ID: 1499755). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 has not been reported in the literature in individuals affected with FHL1-related conditions. This sequence change affects an acceptor splice site in intron 4 of the FHL1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FHL1 are known to be pathogenic (PMID: 18179888, 19687455, 19716112, 22523091, 24114807). This variant is not present in population databases (gnomAD no frequency).

#	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