NM_006790.2(MYOT):c.164C>T (p.Ser55Phe) AND Myofibrillar myopathy 3

Clinical significance:Pathogenic (Last evaluated: Feb 12, 2019)

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_006790.2(MYOT):c.164C>T (p.Ser55Phe)]

NM_006790.2(MYOT):c.164C>T (p.Ser55Phe)

PKD2L2-DT:PKD2L2 divergent transcript [Gene - HGNC]
MYOT:myotilin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_006790.2(MYOT):c.164C>T (p.Ser55Phe)
  • NC_000005.10:g.137870815C>T
  • NG_008894.1:g.7960C>T
  • NM_001135940.2:c.-197+290C>T
  • NM_001300911.2:c.-120-62C>T
  • NM_006790.2:c.164C>T
  • NP_006781.1:p.Ser55Phe
  • LRG_201t1:c.164C>T
  • LRG_201:g.7960C>T
  • LRG_201p1:p.Ser55Phe
  • NC_000005.9:g.137206504C>T
Protein change:
OMIM: 604103.0002; dbSNP: rs121908457
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001135940.2:c.-197+290C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001300911.2:c.-120-62C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_006790.2:c.164C>T - missense variant - [Sequence Ontology: SO:0001583]


Myofibrillar myopathy 3 (MFM3)
MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1; Limb-girdle muscular dystrophy, type 1A; Muscular dystrophy, proximal, type 1A
MONDO: MONDO:0012215; MedGen: C3714934; Orphanet: 266; OMIM: 609200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000026373OMIMno assertion criteria providedPathogenic
(Apr 27, 2004)
germlineliterature only

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

SCV000933950Invitaecriteria provided, single submitter
(Feb 12, 2019)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017.

Straub V, Murphy A, Udd B; LGMD workshop study group..

Neuromuscul Disord. 2018 Aug;28(8):702-710. doi: 10.1016/j.nmd.2018.05.007. Epub 2018 May 24. No abstract available.

PubMed [citation]

myotilin Mutation found in second pedigree with LGMD1A.

Hauser MA, Conde CB, Kowaljow V, Zeppa G, Taratuto AL, Torian UM, Vance J, Pericak-Vance MA, Speer MC, Rosa AL.

Am J Hum Genet. 2002 Dec;71(6):1428-32. Epub 2002 Nov 11.

PubMed [citation]
See all PubMed Citations (11)

Details of each submission

From OMIM, SCV000026373.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)


Hauser et al. (2002) performed a mutation screening of 86 families with a variety of neuromuscular disorders. In an Argentinian family with a diagnosis of limb-girdle muscular dystrophy (LGMD1A), later reclassified as myofibrillar myopathy-3 (MFM3; 609200) by Straub et al. (2018), they identified a TTID mutation predicted to result in the conversion of serine-55 to phenylalanine (S55F). The mutation was located in the unique N-terminal domain of myotilin, only 2 residues from the thr57-to-ile mutation (604103.0001). Both mutations are located outside the alpha-actinin and gamma-filamin binding sites within myotilin.

Selcen and Engel (2004) identified the S55F mutation in a woman with MFM3. The patient had slowly progressive muscle weakness and wasting, distal greater than proximal, and peripheral neuropathy. She had an affected brother with cardiomyopathy and an affected son.

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

From Invitae, SCV000933950.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)


This sequence change replaces serine with phenylalanine at codon 55 of the MYOT protein (p.Ser55Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in many individuals and families affected with myofibrillar myopathy, limb-girdle muscular dystrophy and other forms of myotilinopathies (PMID:12428213, 16684602, 9027924, 26342832, 21676617, 25208129, 15111675, 15947064). ClinVar contains an entry for this variant (Variation ID: 5835). Experimental studies have shown that this missense change exhibits slower degradation rates than wild type myotilin, however the significance of this finding is uncertain (PMID: 21361873). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 6, 2021

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