NM_001159699.2(FHL1):c.417C>A (p.His139Gln) AND X-linked myopathy with postural muscle atrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 6, 2021
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:: RCV001896151.5

Allele description [Variation Report for NM_001159699.2(FHL1):c.417C>A (p.His139Gln)]

NM_001159699.2(FHL1):c.417C>A (p.His139Gln)

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.417C>A (p.His139Gln)

HGVS:

NC_000023.11:g.136207829C>A
NG_015895.1:g.65430C>A
NM_001159699.2:c.417C>AMANE SELECT
NM_001159700.2:c.369C>A
NM_001159701.2:c.456C>A
NM_001159702.3:c.369C>A
NM_001159703.2:c.369C>A
NM_001159704.1:c.369C>A
NM_001167819.1:c.369C>A
NM_001330659.2:c.417C>A
NM_001369326.1:c.369C>A
NM_001369327.2:c.369C>A
NM_001369328.1:c.369C>A
NM_001369329.1:c.369C>A
NM_001369330.1:c.369C>A
NM_001369331.1:c.369C>A
NM_001449.5:c.369C>A
NP_001153171.1:p.His139Gln
NP_001153172.1:p.His123Gln
NP_001153173.1:p.His152Gln
NP_001153174.1:p.His123Gln
NP_001153175.1:p.His123Gln
NP_001153176.1:p.His123Gln
NP_001161291.1:p.His123Gln
NP_001317588.1:p.His139Gln
NP_001356255.1:p.His123Gln
NP_001356256.1:p.His123Gln
NP_001356257.1:p.His123Gln
NP_001356258.1:p.His123Gln
NP_001356259.1:p.His123Gln
NP_001356260.1:p.His123Gln
NP_001440.2:p.His123Gln
LRG_739t1:c.417C>A
LRG_739t2:c.369C>A
LRG_739:g.65430C>A
LRG_739p1:p.His139Gln
LRG_739p2:p.His123Gln
NC_000023.10:g.135289988C>A
NR_027621.2:n.780C>A

Protein change:

H123Q

Links:

dbSNP: rs267606813

NCBI 1000 Genomes Browser:

rs267606813

Molecular consequence:

NM_001159699.2:c.417C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159700.2:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159701.2:c.456C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159702.3:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159703.2:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159704.1:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167819.1:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330659.2:c.417C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369326.1:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369327.2:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369328.1:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369329.1:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369330.1:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369331.1:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001449.5:c.369C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_027621.2:n.780C>A - 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
SCV002159402	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 6, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22094483, 31204143, 19181672, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002159402

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 6, 2021)

germline

clinical testing

PubMed (4)
[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

Reducing bodies and myofibrillar myopathy features in FHL1 muscular dystrophy.

Selcen D, Bromberg MB, Chin SS, Engel AG.

Neurology. 2011 Nov 29;77(22):1951-9. doi: 10.1212/WNL.0b013e31823a0ebe. Epub 2011 Nov 16.

PubMed [citation]

PMID:: 22094483
PMCID:: PMC3235356

Concurrent positive anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase antibody with reducing body myopathy: Possible double trouble.

Tanboon J, Sanmaneechai O, Charuvanij S, Sangruchi T, Galindo-Feria AS, Lundberg IE, Ohnuki Y, Shiina T, Suzuki S, Nishino I.

Neuromuscul Disord. 2019 Jul;29(7):543-548. doi: 10.1016/j.nmd.2019.05.007. Epub 2019 May 23.

PubMed [citation]

PMID:: 31204143

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002159402.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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: 22094483, 31204143; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This sequence change replaces histidine with glutamine at codon 123 of the FHL1 protein (p.His123Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with reducing body myopathy (PMID: 19181672). In at least one individual the variant was observed to be de novo.

#	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

ClinVar

Relating variation to medicine