NM_033337.3(CAV3):c.189_197del (p.Thr64_Thr66del) AND Rippling muscle disease 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 3, 1999
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000008767.7

Allele description [Variation Report for NM_033337.3(CAV3):c.189_197del (p.Thr64_Thr66del)]

NM_033337.3(CAV3):c.189_197del (p.Thr64_Thr66del)

Genes:

CAV3:caveolin 3 [Gene - OMIM - HGNC]
OXTR:oxytocin receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_033337.3(CAV3):c.189_197del (p.Thr64_Thr66del)

HGVS:

NC_000003.12:g.8745600_8745608del
NG_008797.2:g.16791_16799del
NM_001234.5:c.189_197del
NM_033337.3:c.189_197delMANE SELECT
NP_001225.1:p.Thr64_Thr66del
NP_203123.1:p.Thr64_Thr66del
NP_203123.1:p.Thr64_Thr66del
LRG_329t1:c.189_197del
LRG_329:g.16791_16799del
LRG_329p1:p.Thr64_Thr66del
NC_000003.11:g.8787286_8787294del
NM_033337.2:c.189_197del
r.189_197del

Links:

Leiden Muscular Dystrophy (CAV3): CAV3_00002; OMIM: 601253.0002; dbSNP: rs199476331

NCBI 1000 Genomes Browser:

rs199476331

Molecular consequence:

NM_001234.5:c.189_197del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_033337.3:c.189_197del - inframe_deletion - [Sequence Ontology: SO:0001822]

Functional consequence:

functional variant [Sequence Ontology: SO:0001536]

Condition(s)

Name:: Rippling muscle disease 2 (RMD2)
Synonyms:: Limb-girdle muscular dystrophy, type 1C; CAV3-Related Rippling Muscle Disease
Identifiers:: MONDO: MONDO:0019947; MedGen: C1832560; Orphanet: 265; OMIM: 606072

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028976	OMIM	no assertion criteria provided	Pathogenic (Sep 3, 1999)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 9537420, 30055862, 10464299

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028976

OMIM

no assertion criteria provided

Pathogenic
(Sep 3, 1999)

germline

literature only

PubMed (3)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.

Minetti C, Sotgia F, Bruno C, Scartezzini P, Broda P, Bado M, Masetti E, Mazzocco M, Egeo A, Donati MA, Volonte D, Galbiati F, Cordone G, Bricarelli FD, Lisanti MP, Zara F.

Nat Genet. 1998 Apr;18(4):365-8.

PubMed [citation]

PMID:: 9537420

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]

PMID:: 30055862

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000028976.6

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

Description

Minetti et al. (1998) demonstrated that 4 affected members in 3 generations of an Italian family diagnosed with autosomal dominant limb-girdle muscular dystrophy (LGMD1C), which was reclassified by Straub et al. (2018) as rippling muscle disease (RMD2; 606072), had a 9-bp deletion beginning at nucleotide 186 of the CAV3 gene, which resulted in the loss of 3 amino acids (residues 63-65) without changing the open reading frame.

Variant Function

Galbiati et al. (1999) stated that the residues lost in this deletion (TFT) reside within the caveolin scaffolding domain. They found that rat Cav3 with the TFT deletion was excluded from caveolae-enriched membranes, accumulated in the Golgi apparatus, and formed oligomers of much larger size than wildtype Cav3. Mutant Cav3 behaved in a dominant-negative fashion, causing retention of wildtype Cav3 in the Golgi.

#	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

Last Updated: Aug 5, 2023

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