NM_033337.3(CAV3):c.314C>T (p.Pro105Leu) AND Rippling muscle disease 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 2005
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:: RCV000008765.8

Allele description [Variation Report for NM_033337.3(CAV3):c.314C>T (p.Pro105Leu)]

NM_033337.3(CAV3):c.314C>T (p.Pro105Leu)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_033337.3(CAV3):c.314C>T (p.Pro105Leu)

HGVS:

NC_000003.12:g.8745725C>T
NG_008797.2:g.16916C>T
NM_001234.5:c.314C>T
NM_033337.3:c.314C>TMANE SELECT
NP_001225.1:p.Pro105Leu
NP_203123.1:p.Pro105Leu
NP_203123.1:p.Pro105Leu
LRG_329t1:c.314C>T
LRG_329:g.16916C>T
LRG_329p1:p.Pro105Leu
NC_000003.11:g.8787411C>T
NM_033337.2:c.314C>T
P56539:p.Pro105Leu
p.(Pro105Leu)
r.314c>u

Protein change:

P105L; PRO105LEU

Links:

Leiden Muscular Dystrophy (CAV3): CAV3_00001; UniProtKB: P56539#VAR_001403; OMIM: 601253.0001; dbSNP: rs116840805

NCBI 1000 Genomes Browser:

rs116840805

Molecular consequence:

NM_001234.5:c.314C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033337.3:c.314C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000028974	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2005)	germline	literature only	PubMed (6) [See all records that cite these PMIDs] 15580566, 30055862, 9537420, 2705900, 11431690, 10464299

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028974

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 2005)

germline

literature only

PubMed (6)
[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

Molecular and muscle pathology in a series of caveolinopathy patients.

Fulizio L, Nascimbeni AC, Fanin M, Piluso G, Politano L, Nigro V, Angelini C.

Hum Mutat. 2005 Jan;25(1):82-9.

PubMed [citation]

PMID:: 15580566

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 (6)

Details of each submission

From OMIM, SCV000028974.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (6)

Description

The numbering of this CAV3 mutation is based on the numbering system used by Fulizio et al. (2005). Early reports designated this mutation PRO104LEU.

In 4 members over 2 generations of an Italian family diagnosed with limb-girdle muscular dystrophy (LGMD1C), which was reclassified by Straub et al. (2018) as rippling muscle disease (RMD2; 606072), Minetti et al. (1998) identified a heterozygous 311C-to-T transition in the CAV3 gene, resulting in a pro104-to-leu (P104L) substitution.

In family A with rippling muscle disease described by Ricker et al. (1989), Betz et al. (2001) identified the P105L mutation.

Variant Function

Galbiati et al. (1999) stated that P104 resides in the membrane-spanning domain of CAV3. They found that rat Cav3 with the P104L mutation 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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