VCV003728145.1 - ClinVar

NM_001159699.2(FHL1):c.606dup (p.Val203fs)

Germline

Classification

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

Pathogenic

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.606dup (p.Val203fs)

Variation ID: 3728145 Accession: VCV003728145.1

Type and length

Duplication, 1 bp

Location

Cytogenetic: Xq26.3 X: 136208508-136208509 (GRCh38) [ NCBI UCSC ] X: 135290667-135290668 (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	Feb 26, 2025	Feb 25, 2025	Dec 27, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001159699.2:c.606dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001153171.1:p.Val203fs	frameshift
NM_001159702.3:c.558dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001153174.1:p.Val187fs	frameshift
NM_001159700.2:c.558dup	NP_001153172.1:p.Val187fs	frameshift
NM_001159701.2:c.645dup	NP_001153173.1:p.Val216fs	frameshift
NM_001159703.2:c.501+550dup		intron variant
NM_001159704.1:c.558dup	NP_001153176.1:p.Val187fs	frameshift
NM_001167819.1:c.558dup	NP_001161291.1:p.Val187fs	frameshift
NM_001330659.2:c.549+550dup		intron variant
NM_001369326.1:c.558dup	NP_001356255.1:p.Val187fs	frameshift
NM_001369327.2:c.558dup	NP_001356256.1:p.Val187fs	frameshift
NM_001369328.1:c.558dup	NP_001356257.1:p.Val187fs	frameshift
NM_001369329.1:c.558dup	NP_001356258.1:p.Val187fs	frameshift
NM_001369330.1:c.558dup	NP_001356259.1:p.Val187fs	frameshift
NM_001369331.1:c.558dup	NP_001356260.1:p.Val187fs	frameshift
NM_001449.5:c.558dup	NP_001440.2:p.Val187fs	frameshift
NR_027621.2:n.969dup		non-coding transcript variant
NC_000023.11:g.136208511dup
NC_000023.10:g.135290670dup
NG_015895.1:g.66112dup
LRG_739:g.66112dup
LRG_739t1:c.606dup	LRG_739p1:p.Val203fs
LRG_739t2:c.558dup	LRG_739p2:p.Val187fs

... more HGVS ... less HGVS

Protein change

V187fs, V216fs, V203fs

Other names

Canonical SPDI

NC_000023.11:136208508:TTT:TTTT

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.

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

Links

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	631	808

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	Pathogenic (1)	criteria provided, single submitter	Dec 27, 2024	RCV005205944.1

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.
Pathogenic (Dec 27, 2024) 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: SCV005844052.1 First in ClinVar: Feb 25, 2025 Last updated: Feb 25, 2025	Publications: PubMed (5) PubMed: 18179888‚ 19687455‚ 19716112‚ 22523091‚ 24114807 Comment: show This sequence change creates a premature translational stop signal (p.Val187Cysfs*7) in the FHL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FHL1 are known to be pathogenic (PMID: 18179888, 19687455, 19716112, 22523091, 24114807). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FHL1-related conditions. For these reasons, this variant has been classified as 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 creates a premature translational stop signal (p.Val187Cysfs*7) in the FHL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FHL1 are known to be pathogenic (PMID: 18179888, 19687455, 19716112, 22523091, 24114807). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FHL1-related conditions. For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Isolated X-linked hypertrophic cardiomyopathy caused by a novel mutation of the four-and-a-half LIM domain 1 gene.	Hartmannova H	Circulation. Cardiovascular genetics	2013	PMID: 24114807
Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy.	Friedrich FW	Human molecular genetics	2012	PMID: 22523091
Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.	Gueneau L	American journal of human genetics	2009	PMID: 19716112
Consequences of mutations within the C terminus of the FHL1 gene.	Schoser B	Neurology	2009	PMID: 19687455
An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1.	Windpassinger C	American journal of human genetics	2008	PMID: 18179888

Text-mined citations for this variant ...

Record last updated May 19, 2025

ClinVar Genomic variation as it relates to human health

NM_001159699.2(FHL1):c.606dup (p.Val203fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for this variant ...