VCV000943902.9 - ClinVar

NM_001159699.2(FHL1):c.498C>G (p.Cys166Trp)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely pathogenic
Likely pathogenic (1)

This classification is based on the single submission received

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001159699.2(FHL1):c.498C>G (p.Cys166Trp)

Variation ID: 943902 Accession: VCV000943902.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq26.3 X: 136207910 (GRCh38) [ NCBI UCSC ] X: 135290069 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 16, 2020	Feb 15, 2026	Sep 24, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001159699.2:c.498C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001153171.1:p.Cys166Trp	missense
NM_001159702.3:c.450C>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001153174.1:p.Cys150Trp	missense
NM_001159700.2:c.450C>G	NP_001153172.1:p.Cys150Trp	missense
NM_001159701.2:c.537C>G	NP_001153173.1:p.Cys179Trp	missense
NM_001159703.2:c.450C>G	NP_001153175.1:p.Cys150Trp	missense
NM_001159704.1:c.450C>G	NP_001153176.1:p.Cys150Trp	missense
NM_001167819.1:c.450C>G	NP_001161291.1:p.Cys150Trp	missense
NM_001330659.2:c.498C>G	NP_001317588.1:p.Cys166Trp	missense
NM_001369326.1:c.450C>G	NP_001356255.1:p.Cys150Trp	missense
NM_001369327.2:c.450C>G	NP_001356256.1:p.Cys150Trp	missense
NM_001369328.1:c.450C>G	NP_001356257.1:p.Cys150Trp	missense
NM_001369329.1:c.450C>G	NP_001356258.1:p.Cys150Trp	missense
NM_001369330.1:c.450C>G	NP_001356259.1:p.Cys150Trp	missense
NM_001369331.1:c.450C>G	NP_001356260.1:p.Cys150Trp	missense
NM_001449.5:c.450C>G	NP_001440.2:p.Cys150Trp	missense
NR_027621.2:n.861C>G		non-coding transcript variant
NC_000023.11:g.136207910C>G
NC_000023.10:g.135290069C>G
NG_015895.1:g.65511C>G
LRG_739:g.65511C>G
LRG_739t1:c.498C>G	LRG_739p1:p.Cys166Trp
LRG_739t2:c.450C>G	LRG_739p2:p.Cys150Trp

... more HGVS ... less HGVS

Protein change

C166W, C150W, C179W

Other names

Canonical SPDI

NC_000023.11:136207909:C:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00503 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA414608558 dbSNP: rs145445372 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
FHL1		-	-	GRCh38 GRCh37	674	858

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
X-linked myopathy with postural muscle atrophy	Likely pathogenic (1)	criteria provided, single submitter	Sep 24, 2025	RCV001214185.10

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Sep 24, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	X-linked myopathy with postural muscle atrophy	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001385856.7 First in ClinVar: Jul 16, 2020 Last updated: Feb 15, 2026	Publications: PubMed (4) PubMed: 19171836‚ 20571991‚ 23169582‚ 25191266 Comment: show This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 150 of the FHL1 protein (p.Cys150Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked dominant FHL1-related conditions (internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 943902). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Cys150 amino acid residue in FHL1. Other variant(s) that disrupt this residue have been observed in individuals with FHL1-related conditions (PMID: 19171836, 20571991, 23169582, 25191266), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 150 of the FHL1 protein (p.Cys150Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked dominant FHL1-related conditions (internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 943902). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Cys150 amino acid residue in FHL1. Other variant(s) that disrupt this residue have been observed in individuals with FHL1-related conditions (PMID: 19171836, 20571991, 23169582, 25191266), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Aggresome-Autophagy Involvement in a Sarcopenic Patient with Rigid Spine Syndrome and a p.C150R Mutation in FHL1 Gene.	Sabatelli P	Frontiers in aging neuroscience	2014	PMID: 25191266
Novel FHL1 mutation in a family with reducing body myopathy.	Schreckenbach T	Muscle & nerve	2013	PMID: 23169582
Familial reducing body myopathy with cytoplasmic bodies and rigid spine revisited: identification of a second LIM domain mutation in FHL1.	Schessl J	Neuropediatrics	2010	PMID: 20571991
Novel FHL1 mutations in fatal and benign reducing body myopathy.	Shalaby S	Neurology	2009	PMID: 19171836

Text-mined citations for rs145445372 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026