NM_006790.3(MYOT):c.116C>T (p.Ser39Phe) AND Myofibrillar myopathy 3

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Aug 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002512824.13

Allele description [Variation Report for NM_006790.3(MYOT):c.116C>T (p.Ser39Phe)]

NM_006790.3(MYOT):c.116C>T (p.Ser39Phe)

Genes:

PKD2L2-DT:PKD2L2 divergent transcript [Gene - HGNC]
MYOT:myotilin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.2

Genomic location:

Preferred name:

NM_006790.3(MYOT):c.116C>T (p.Ser39Phe)

HGVS:

NC_000005.10:g.137870767C>T
NG_008894.1:g.7912C>T
NM_001135940.2:c.-197+242C>T
NM_001300911.2:c.-120-110C>T
NM_006790.3:c.116C>TMANE SELECT
NP_006781.1:p.Ser39Phe
NP_006781.1:p.Ser39Phe
LRG_201t1:c.116C>T
LRG_201:g.7912C>T
LRG_201p1:p.Ser39Phe
NC_000005.9:g.137206456C>T
NM_006790.2:c.116C>T

Protein change:

S39F; SER39PHE

Links:

OMIM: 604103.0006; dbSNP: rs121908461

NCBI 1000 Genomes Browser:

rs121908461

Molecular consequence:

NM_001135940.2:c.-197+242C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001300911.2:c.-120-110C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_006790.3:c.116C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Myofibrillar myopathy 3 (MFM3)
Synonyms:: Limb-girdle muscular dystrophy, type 1A; Muscular dystrophy, proximal, type 1A; Spheroid body myopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012215; MedGen: C3714934; Orphanet: 266; Orphanet: 268129; OMIM: 609200

Recent activity

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unnamed protein product [Albugo candida]
unnamed protein product [Albugo candida]
gi|635360496|emb|CCI50233.1|

Protein
ugt1a5 UDP glucuronosyltransferase 1 family, polypeptide A5 [Danio rerio]
ugt1a5 UDP glucuronosyltransferase 1 family, polypeptide A5 [Danio rerio]
Gene ID:100384897

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026378	OMIM	no assertion criteria provided	Pathogenic (Dec 27, 2005)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 571956, 16380616
SCV003439235	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 11, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16380616, 22106715, 28492532
SCV004238301	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000026378

OMIM

no assertion criteria provided

Pathogenic
(Dec 27, 2005)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV003439235

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 11, 2022)

germline

clinical testing

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

SCV004238301

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 14, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Autosomal dominant "spheroid body myopathy".

Goebel HH, Muller J, Gillen HW, Merritt AD.

Muscle Nerve. 1978 Jan-Feb;1(1):14-26.

PubMed [citation]

PMID:: 571956

A mutation in myotilin causes spheroid body myopathy.

Foroud T, Pankratz N, Batchman AP, Pauciulo MW, Vidal R, Miravalle L, Goebel HH, Cushman LJ, Azzarelli B, Horak H, Farlow M, Nichols WC.

Neurology. 2005 Dec 27;65(12):1936-40.

PubMed [citation]

PMID:: 16380616

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000026378.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In 21 affected members of a large kindred with myofibrillar myopathy-3 (MFM3; 609200), originally reported as 'spheroid body myopathy' by Goebel et al. (1978), Foroud et al. (2005) identified a heterozygous 116C-T transition in exon 2 of the TTID gene, resulting in a ser39-to-phe (S39F) substitution. The mutation was not identified in 135 control individuals.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439235.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 39 of the MYOT protein (p.Ser39Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with MYOT-related conditions (PMID: 16380616, 22106715). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5839).

#	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

From Revvity Omics, Revvity, SCV004238301.1

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

#	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: Oct 13, 2024

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