NM_001159699.2(FHL1):c.797dup (p.His267fs) AND X-linked myopathy with postural muscle atrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 7, 2024
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:: RCV005153536.1

Allele description [Variation Report for NM_001159699.2(FHL1):c.797dup (p.His267fs)]

NM_001159699.2(FHL1):c.797dup (p.His267fs)

Gene:

FHL1:four and a half LIM domains 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

Xq26.3

Genomic location:

Preferred name:

NM_001159699.2(FHL1):c.797dup (p.His267fs)

HGVS:

NC_000023.11:g.136209931dup
NG_015895.1:g.67532dup
NM_001159699.2:c.797dupMANE SELECT
NM_001159700.2:c.749dup
NM_001159701.2:c.836dup
NM_001159702.3:c.949dup
NM_001159703.2:c.562dup
NM_001159704.1:c.749dup
NM_001167819.1:c.749dup
NM_001330659.2:c.610dup
NM_001369326.1:c.949dup
NM_001369327.2:c.949dup
NM_001369328.1:c.949dup
NM_001369329.1:c.749dup
NM_001369330.1:c.749dup
NM_001369331.1:c.749dup
NM_001449.5:c.749dup
NP_001153171.1:p.His267fs
NP_001153172.1:p.His251fs
NP_001153173.1:p.His280fs
NP_001153174.1:p.Ser317fs
NP_001153175.1:p.Ser188fs
NP_001153176.1:p.His251fs
NP_001161291.1:p.His251fs
NP_001317588.1:p.Ser204fs
NP_001356255.1:p.Ser317fs
NP_001356256.1:p.Ser317fs
NP_001356257.1:p.Ser317fs
NP_001356258.1:p.His251fs
NP_001356259.1:p.His251fs
NP_001356260.1:p.His251fs
NP_001440.2:p.His251fs
LRG_739t1:c.797dup
LRG_739t2:c.949dup
LRG_739:g.67532dup
LRG_739p1:p.His267fs
LRG_739p2:p.Ser317fs
NC_000023.10:g.135292088_135292089insT
NC_000023.10:g.135292090dup
NR_027621.2:n.1160dup

Protein change:

H251fs

Molecular consequence:

NM_001159699.2:c.797dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159700.2:c.749dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159701.2:c.836dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159702.3:c.949dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159703.2:c.562dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159704.1:c.749dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167819.1:c.749dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330659.2:c.610dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369326.1:c.949dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369327.2:c.949dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369328.1:c.949dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369329.1:c.749dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369330.1:c.749dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369331.1:c.749dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001449.5:c.749dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027621.2:n.1160dup - 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
SCV005777007	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 7, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19716112, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005777007

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 7, 2024)

germline

clinical testing

PubMed (2)
[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

Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.

Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M, Hoeltzenbein M, Spuler S, Saitoh S, Verschueren A, Tranchant C, Beuvin M, Lacene E, Romero NB, Heath S, Zelenika D, Voit T, Eymard B, Ben Yaou R, Bonne G.

Am J Hum Genet. 2009 Sep;85(3):338-53. doi: 10.1016/j.ajhg.2009.07.015. Epub 2009 Aug 27.

PubMed [citation]

PMID:: 19716112
PMCID:: PMC2771595

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005777007.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change results in a frameshift in the FHL1 gene (p.His251Profs*33). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 30 amino acid(s) of the FHL1 protein and extend the protein by 2 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FHL1-related conditions. This variant disrupts a region of the FHL1 protein in which other variant(s) (p.Cys276Tyr) have been determined to be pathogenic (PMID: 19716112). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it 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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