NM_001159699.2(FHL1):c.801delinsAA (p.His267fs) AND X-linked myopathy with postural muscle atrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 22, 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:: RCV002725419.3

Allele description [Variation Report for NM_001159699.2(FHL1):c.801delinsAA (p.His267fs)]

NM_001159699.2(FHL1):c.801delinsAA (p.His267fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

Xq26.3

Genomic location:

Preferred name:

NM_001159699.2(FHL1):c.801delinsAA (p.His267fs)

HGVS:

NC_000023.11:g.136209935delinsAA
NG_015895.1:g.67536delinsAA
NM_001159699.2:c.801delinsAAMANE SELECT
NM_001159700.2:c.753delinsAA
NM_001159701.2:c.840delinsAA
NM_001159702.3:c.953delinsAA
NM_001159703.2:c.566delinsAA
NM_001159704.1:c.753delinsAA
NM_001167819.1:c.753delinsAA
NM_001330659.2:c.614delinsAA
NM_001369326.1:c.953delinsAA
NM_001369327.2:c.953delinsAA
NM_001369328.1:c.953delinsAA
NM_001369329.1:c.753delinsAA
NM_001369330.1:c.753delinsAA
NM_001369331.1:c.753delinsAA
NM_001449.5:c.753delinsAA
NP_001153171.1:p.His267fs
NP_001153172.1:p.His251fs
NP_001153173.1:p.His280fs
NP_001153174.1:p.Thr318fs
NP_001153175.1:p.Thr189fs
NP_001153176.1:p.His251fs
NP_001161291.1:p.His251fs
NP_001317588.1:p.Thr205fs
NP_001356255.1:p.Thr318fs
NP_001356256.1:p.Thr318fs
NP_001356257.1:p.Thr318fs
NP_001356258.1:p.His251fs
NP_001356259.1:p.His251fs
NP_001356260.1:p.His251fs
NP_001440.2:p.His251fs
LRG_739t1:c.801delinsAA
LRG_739t2:c.953delinsAA
LRG_739:g.67536delinsAA
LRG_739p1:p.His267fs
LRG_739p2:p.Thr318fs
NC_000023.10:g.135292094delinsAA
NR_027621.2:n.1164delinsAA

Protein change:

H251fs

Molecular consequence:

NM_001159699.2:c.801delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159700.2:c.753delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159701.2:c.840delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159702.3:c.953delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159703.2:c.566delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159704.1:c.753delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167819.1:c.753delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330659.2:c.614delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369326.1:c.953delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369327.2:c.953delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369328.1:c.953delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369329.1:c.753delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369330.1:c.753delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369331.1:c.753delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001449.5:c.753delinsAA - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027621.2:n.1164delinsAA - 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

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
SCV002995460	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 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

SCV002995460

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 22, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002995460.2

#	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.His251Glnfs*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. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. 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: Sep 29, 2024

ClinVar

Relating variation to medicine