NM_001159699.2(FHL1):c.812G>C (p.Cys271Ser) AND Myopathy with postural muscle atrophy, X-linked

Clinical significance:Pathogenic (Last evaluated: Jul 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_001159699.2(FHL1):c.812G>C (p.Cys271Ser)]

NM_001159699.2(FHL1):c.812G>C (p.Cys271Ser)

FHL1:four and a half LIM domains 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001159699.2(FHL1):c.812G>C (p.Cys271Ser)
  • NC_000023.11:g.136209946G>C
  • NG_015895.1:g.67547G>C
  • NM_001159699.2:c.812G>CMANE SELECT
  • NM_001159700.2:c.764G>C
  • NM_001159701.2:c.851G>C
  • NM_001159702.3:c.964G>C
  • NM_001159703.2:c.577G>C
  • NM_001159704.1:c.764G>C
  • NM_001167819.1:c.764G>C
  • NM_001330659.2:c.625G>C
  • NM_001369326.1:c.964G>C
  • NM_001369327.1:c.964G>C
  • NM_001369328.1:c.964G>C
  • NM_001369329.1:c.764G>C
  • NM_001369330.1:c.764G>C
  • NM_001369331.1:c.764G>C
  • NM_001449.5:c.764G>C
  • NP_001153171.1:p.Cys271Ser
  • NP_001153172.1:p.Cys255Ser
  • NP_001153173.1:p.Cys284Ser
  • NP_001153174.1:p.Ala322Pro
  • NP_001153175.1:p.Ala193Pro
  • NP_001153176.1:p.Cys255Ser
  • NP_001161291.1:p.Cys255Ser
  • NP_001317588.1:p.Ala209Pro
  • NP_001356255.1:p.Ala322Pro
  • NP_001356256.1:p.Ala322Pro
  • NP_001356257.1:p.Ala322Pro
  • NP_001356258.1:p.Cys255Ser
  • NP_001356259.1:p.Cys255Ser
  • NP_001356260.1:p.Cys255Ser
  • NP_001440.2:p.Cys255Ser
  • LRG_739t1:c.812G>C
  • LRG_739t2:c.964G>C
  • LRG_739:g.67547G>C
  • LRG_739p1:p.Cys271Ser
  • LRG_739p2:p.Ala322Pro
  • NC_000023.10:g.135292105G>C
  • NM_001449.4:c.764G>C
  • NR_027621.1:n.1175G>C
Protein change:
dbSNP: rs869025431
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001159699.2:c.812G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159700.2:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159701.2:c.851G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159702.3:c.964G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159703.2:c.577G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001159704.1:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167819.1:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330659.2:c.625G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369326.1:c.964G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369327.1:c.964G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369328.1:c.964G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369329.1:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369330.1:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369331.1:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001449.5:c.764G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027621.1:n.1175G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Myopathy with postural muscle atrophy, X-linked (XMPMA)
MONDO: MONDO:0010401; MedGen: C2678055; OMIM: 300696

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000963270Invitaecriteria provided, single submitter
(Jul 1, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001423261GenomeConnect, ClinGenno assertion providednot providedunknownphenotyping only

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedphenotyping only



Unclassifiable arrhythmic cardiomyopathy associated with Emery-Dreifuss caused by a mutation in FHL1.

San Román I, Navarro M, Martínez F, Albert L, Polo L, Guardiola J, García-Molina E, Muñoz-Esparza C, López-Ayala JM, Sabater-Molina M, Gimeno JR.

Clin Genet. 2016 Aug;90(2):171-6. doi: 10.1111/cge.12760. Epub 2016 Mar 23.

PubMed [citation]

X-linked Recessive Distal Myopathy With Hypertrophic Cardiomyopathy Caused by a Novel Mutation in the FHL1 Gene.

D'Arcy C, Kanellakis V, Forbes R, Wilding B, McGrath M, Howell K, Ryan M, McLean C.

J Child Neurol. 2015 Aug;30(9):1211-7. doi: 10.1177/0883073814549807. Epub 2014 Sep 22.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000963270.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change replaces cysteine with serine at codon 255 of the FHL1 protein (p.Cys255Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Emery-Dreifuss muscular dystrophy and hypertrophic cardiomyopathy in a family (PMID: 26857240) and with distal myopathy and hypertrophic cardiomyopathy in a different family (PMID: 25246303). ClinVar contains an entry for this variant (Variation ID: 222635). 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 C0). For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GenomeConnect, ClinGen, SCV001423261.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedphenotyping onlynot provided


Variant interpretted as Likely pathogenic and reported on 01-11-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 23, 2021

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