NM_001159699.2(FHL1):c.857_870dup (p.Asp291fs) AND X-linked myopathy with postural muscle atrophy

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 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:: RCV003625707.1

Allele description

NM_001159699.2(FHL1):c.857_870dup (p.Asp291fs)

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.857_870dup (p.Asp291fs)

HGVS:

NC_000023.11:g.136209991_136210004dup
NG_015895.1:g.67592_67605dup
NM_001159699.2:c.857_870dupMANE SELECT
NM_001159700.2:c.809_822dup
NM_001159701.2:c.896_909dup
NM_001159702.3:c.*37_*50dup
NM_001159703.2:c.*37_*50dup
NM_001159704.1:c.809_822dup
NM_001167819.1:c.809_822dup
NM_001330659.2:c.*37_*50dup
NM_001369326.1:c.*37_*50dup
NM_001369327.2:c.*37_*50dup
NM_001369328.1:c.*37_*50dup
NM_001369329.1:c.809_822dup
NM_001369330.1:c.809_822dup
NM_001369331.1:c.809_822dup
NM_001449.5:c.809_822dup
NP_001153171.1:p.Asp291fs
NP_001153172.1:p.Asp275fs
NP_001153173.1:p.Asp304fs
NP_001153176.1:p.Asp275fs
NP_001161291.1:p.Asp275fs
NP_001356258.1:p.Asp275fs
NP_001356259.1:p.Asp275fs
NP_001356260.1:p.Asp275fs
NP_001440.2:p.Asp275fs
LRG_739t1:c.857_870dup
LRG_739t2:c.*37_*50dup
LRG_739:g.67592_67605dup
LRG_739p1:p.Asp291fs
NC_000023.10:g.135292148_135292149insCAAGTGTATTGTCC
NC_000023.10:g.135292150_135292163dup
NR_027621.2:n.1220_1233dup

Protein change:

D275fs

Molecular consequence:

NM_001159702.3:c.*37_*50dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001159703.2:c.*37_*50dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001330659.2:c.*37_*50dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369326.1:c.*37_*50dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369327.2:c.*37_*50dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369328.1:c.*37_*50dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001159699.2:c.857_870dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159700.2:c.809_822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159701.2:c.896_909dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159704.1:c.809_822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167819.1:c.809_822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369329.1:c.809_822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369330.1:c.809_822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369331.1:c.809_822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001449.5:c.809_822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027621.2:n.1220_1233dup - 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

Recent activity

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BJ032131 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clon...
BJ032131 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clone XL015l12 5', mRNA sequence
gi|17378127|gnl|dbEST|10473276|dbj| 131.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004500446	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 3, 2023)	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

SCV004500446

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 3, 2023)

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 Invitae, SCV004500446.1

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

Description

For these reasons, this variant has been classified as Pathogenic. 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. This variant has not been reported in the literature in individuals affected with FHL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the FHL1 gene (p.Asp275Lysfs*20). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acid(s) of the FHL1 protein and extend the protein by 13 additional amino acid residues.

#	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: Feb 28, 2024

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