NM_006790.3(MYOT):c.683+1G>C AND Myofibrillar myopathy 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 26, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002021636.5

Allele description [Variation Report for NM_006790.3(MYOT):c.683+1G>C]

NM_006790.3(MYOT):c.683+1G>C

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.683+1G>C

HGVS:

NC_000005.10:g.137880866G>C
NG_008894.1:g.18011G>C
NM_001135940.2:c.131+1G>C
NM_001300911.2:c.338+1G>C
NM_006790.3:c.683+1G>CMANE SELECT
LRG_201:g.18011G>C
NC_000005.9:g.137216555G>C

Links:

dbSNP: rs2149985981

NCBI 1000 Genomes Browser:

rs2149985981

Molecular consequence:

NM_001135940.2:c.131+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001300911.2:c.338+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_006790.3:c.683+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002313025	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 26, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16199547, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002313025

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 26, 2021)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002313025.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MYOT-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 5 of the MYOT gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYOT cause disease.

#	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: Mar 5, 2024

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