NM_001159699.2(FHL1):c.416A>G (p.His139Arg) 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:: Nov 16, 2022
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:: RCV000646184.6

Allele description

NM_001159699.2(FHL1):c.416A>G (p.His139Arg)

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.416A>G (p.His139Arg)

HGVS:

NC_000023.11:g.136207828A>G
NG_015895.1:g.65429A>G
NM_001159699.2:c.416A>GMANE SELECT
NM_001159700.2:c.368A>G
NM_001159701.2:c.455A>G
NM_001159702.3:c.368A>G
NM_001159703.2:c.368A>G
NM_001159704.1:c.368A>G
NM_001167819.1:c.368A>G
NM_001330659.2:c.416A>G
NM_001369326.1:c.368A>G
NM_001369327.2:c.368A>G
NM_001369328.1:c.368A>G
NM_001369329.1:c.368A>G
NM_001369330.1:c.368A>G
NM_001369331.1:c.368A>G
NM_001449.5:c.368A>G
NP_001153171.1:p.His139Arg
NP_001153172.1:p.His123Arg
NP_001153173.1:p.His152Arg
NP_001153174.1:p.His123Arg
NP_001153175.1:p.His123Arg
NP_001153176.1:p.His123Arg
NP_001161291.1:p.His123Arg
NP_001317588.1:p.His139Arg
NP_001356255.1:p.His123Arg
NP_001356256.1:p.His123Arg
NP_001356257.1:p.His123Arg
NP_001356258.1:p.His123Arg
NP_001356259.1:p.His123Arg
NP_001356260.1:p.His123Arg
NP_001440.2:p.His123Arg
LRG_739t1:c.416A>G
LRG_739t2:c.368A>G
LRG_739:g.65429A>G
LRG_739p1:p.His139Arg
LRG_739p2:p.His123Arg
NC_000023.10:g.135289987A>G
NM_001449.4:c.368A>G
NR_027621.2:n.779A>G

Protein change:

H123R

Links:

dbSNP: rs267606812

NCBI 1000 Genomes Browser:

rs267606812

Molecular consequence:

NM_001159699.2:c.416A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159700.2:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159701.2:c.455A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159702.3:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159703.2:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001159704.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167819.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330659.2:c.416A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369326.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369327.2:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369328.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369329.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369330.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369331.1:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001449.5:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_027621.2:n.779A>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

Recent activity

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PRDX6, partial [Meliphaga gracilis]
PRDX6, partial [Meliphaga gracilis]
gi|1282181066|gb|ATY49970.1|

Protein
NADH dehydrogenase subunit 2, partial (mitochondrion) [Meliphaga gracilis]
NADH dehydrogenase subunit 2, partial (mitochondrion) [Meliphaga gracilis]
gi|1282180532|gb|ATY49703.1|

Protein
brain derived neurotrophic factor, partial [Meliphaga gracilis]
brain derived neurotrophic factor, partial [Meliphaga gracilis]
gi|1282181298|gb|ATY50086.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000767943	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 16, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 18274675, 19181672, 24634512, 22094483, 31204143, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000767943

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 16, 2022)

germline

clinical testing

PubMed (6)
[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

Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.

Schessl J, Taratuto AL, Sewry C, Battini R, Chin SS, Maiti B, Dubrovsky AL, Erro MG, Espada G, Robertella M, Saccoliti M, Olmos P, Bridges LR, Standring P, Hu Y, Zou Y, Swoboda KJ, Scavina M, Goebel HH, Mitchell CA, Flanigan KM, Muntoni F, et al.

Brain. 2009 Feb;132(Pt 2):452-64. doi: 10.1093/brain/awn325. Epub 2009 Jan 29.

PubMed [citation]

PMID:: 19181672
PMCID:: PMC2724920

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000767943.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His123 amino acid residue in FHL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18274675, 19181672, 24634512). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 537353). This missense change has been observed in individual(s) with X-linked dominant reducing body myopathy (PMID: 22094483, 31204143; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 123 of the FHL1 protein (p.His123Arg).

#	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 20, 2024

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