NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del) AND RYR1-related disorder

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 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:: RCV001970803.3

Allele description

NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)

Gene:

RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)

HGVS:

NC_000019.10:g.38543856TGA[2]
NC_000019.9:g.39034502_39034504del
NG_008866.1:g.115157TGA[2]
NM_000540.3:c.11993TGA[2]MANE SELECT
NM_001042723.2:c.11978TGA[2]
NP_000531.2:p.Met4000del
NP_001036188.1:p.Met3995del
LRG_766:g.115157TGA[2]
NC_000019.9:g.39034495_39034497del
NC_000019.9:g.39034496TGA[2]
NC_000019.9:g.39034502_39034504del

Protein change:

M3995del

Links:

dbSNP: rs2145776584

NCBI 1000 Genomes Browser:

rs2145776584

Molecular consequence:

NM_000540.3:c.11993TGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001042723.2:c.11978TGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: RYR1-related disorder
Synonyms:: RYR1-Related Disorders; RYR1-related condition
Identifiers:: MedGen: CN239331

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002260609	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30611313, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002260609

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 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

'Dusty core disease' (DuCD): expanding morphological spectrum of RYR1 recessive myopathies.

Garibaldi M, Rendu J, Brocard J, Lacene E, Fauré J, Brochier G, Beuvin M, Labasse C, Madelaine A, Malfatti E, Bevilacqua JA, Lubieniecki F, Monges S, Taratuto AL, Laporte J, Marty I, Antonini G, Romero NB.

Acta Neuropathol Commun. 2019 Jan 5;7(1):3. doi: 10.1186/s40478-018-0655-5.

PubMed [citation]

PMID:: 30611313
PMCID:: PMC6320585

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002260609.3

#	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with clinical features of autosomal recessive RYR1-related conditions (PMID: 30611313). This variant is not present in population databases (ExAC no frequency). This variant, c.11999_12001del, results in the deletion of 1 amino acid(s) of the RYR1 protein (p.Met4000del), but otherwise preserves the integrity of the reading frame.

#	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: May 19, 2024

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