NM_006790.3(MYOT):c.179C>G (p.Ser60Cys) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 22, 2022
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:: RCV000725007.22

Allele description [Variation Report for NM_006790.3(MYOT):c.179C>G (p.Ser60Cys)]

NM_006790.3(MYOT):c.179C>G (p.Ser60Cys)

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.179C>G (p.Ser60Cys)

HGVS:

NC_000005.10:g.137870830C>G
NG_008894.1:g.7975C>G
NM_001135940.2:c.-197+305C>G
NM_001300911.2:c.-120-47C>G
NM_006790.3:c.179C>GMANE SELECT
NP_006781.1:p.Ser60Cys
NP_006781.1:p.Ser60Cys
LRG_201t1:c.179C>G
LRG_201:g.7975C>G
LRG_201p1:p.Ser60Cys
NC_000005.9:g.137206519C>G
NM_006790.2:c.179C>G
p.Ser60Cys

Protein change:

S60C; SER60CYS

Links:

OMIM: 604103.0003; dbSNP: rs121908458

NCBI 1000 Genomes Browser:

rs121908458

Molecular consequence:

NM_001135940.2:c.-197+305C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001300911.2:c.-120-47C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_006790.3:c.179C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000333146	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Oct 13, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001714143	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 8, 2020)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 15111675, 21676617, 21361873, 22349301, 19225410, 17784878, 27618136, 32041727, 25741868
SCV001812081	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 22, 2022)	germline	clinical testing	Citation Link,
SCV002770883	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Sep 7, 2017)	unknown	clinical testing	PubMed (11) [See all records that cite these PMIDs] 15947064, 17931355, 17784878, 27618136, 26842778, 22021208, 15111675, 22349301, 21676617, 21361873, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	21	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

TAR DNA-Binding protein 43 accumulation in protein aggregate myopathies.

Olivé M, Janué A, Moreno D, Gámez J, Torrejón-Escribano B, Ferrer I.

J Neuropathol Exp Neurol. 2009 Mar;68(3):262-73. doi: 10.1097/NEN.0b013e3181996d8f.

PubMed [citation]

PMID:: 19225410

Clinical Reasoning: A case of bilateral foot drop in a 74-year-old man.

Harada Y, Zuchner SL, Herrmann DN, Veerapandiyan A.

Neurology. 2020 Mar 3;94(9):405-409. doi: 10.1212/WNL.0000000000008760. Epub 2020 Feb 10. No abstract available.

PubMed [citation]

PMID:: 32041727
PMCID:: PMC7238946

See all PubMed Citations (14)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000333146.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	19	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		19	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714143.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (9)

Description

PS3, PS4_moderate, PM2, PP4, PP5

#	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		2	not provided	not provided	not provided

From GeneDx, SCV001812081.3

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

Description

Published functional studies demonstrate reduced degradation of myotilin (von Nandelstadh et al., 2011); Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22349301, 15947064, 21676617, 15111675, 27618136, 21361873, 32403337, 32041727)

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

From Athena Diagnostics Inc, SCV002770883.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant affected protein organization in muscle cells (PMID: 22349301).

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

Last Updated: May 1, 2024

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