Activity

Filter

Cancel
Date Panel Item Activity
26 actions
Rhabdomyolysis and metabolic muscle disorders v6.9 CAV3 Ida Ertmanska changed review comment from: Comment on mode of inheritance: There are 7 families reported in literature with biallelic CAV3 variants and features of a metabolic muscle disorder. Only 2 patients harbouring the same variant p.Ala93Thr presented with severe rippling muscle disease (PMIDs: 12666119; 15668980). Other individuals had variable presentations including isolated exercise intolerance (1), limb girdle muscular dystrophy (1), and mild proximal muscle weakness (2). One individual was asymptomatic at 49 years. In addition, 2/7 cases harboured Likely Benign variants with homozygotes reported in gnomAD (PMIDs: 9536092; 18253147). Hence, mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted, due to conflicting evidence for a BIALLELIC association. An 'expert-review' tag was added to obtain a second opinion on this proposed change.; to: Comment on mode of inheritance: There are 7 families reported in literature with biallelic CAV3 variants and features of a metabolic muscle disorder. Only 2 patients harbouring the same variant p.Ala93Thr presented with severe rippling muscle disease (PMIDs: 12666119; 15668980). Other individuals had variable presentations including isolated exercise intolerance (1), limb girdle muscular dystrophy (1), and mild proximal muscle weakness (2). One individual was asymptomatic at 49 years. In addition, 2/7 cases harboured Likely Benign variants with homozygotes reported in gnomAD (PMIDs: 9536092; 18253147). Hence, mode of inheritance should remain MONOALLELIC, due to conflicting evidence for a BIALLELIC association. A 'watchlist-moi' tag was added in anticipation of stronger evidence for the recessive assocation.
Rhabdomyolysis and metabolic muscle disorders v6.9 CAV3 Ida Ertmanska changed review comment from: Comment on mode of inheritance: There are 7 families reported in literature with biallelic CAV3 variants and features of a metabolic muscle disorder. Only 2 patients harbouring the same variant p.Ala93Thr presented with severe rippling muscle disease (PMIDs: 12666119; 15668980). Other individuals had variable presentations including isolated exercise intolerance, limb girdle muscular dystrophy, and mild proximal muscle weakness. One individual was asymptomatic at 49 years. In addition, 2/7 cases harboured Likely Benign variants with homozygotes reported in gnomAD (PMIDs: 9536092; 18253147). Hence, mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted, due to conflicting evidence for a BIALLELIC association. An 'expert-review' tag was added to obtain a second opinion on this proposed change.; to: Comment on mode of inheritance: There are 7 families reported in literature with biallelic CAV3 variants and features of a metabolic muscle disorder. Only 2 patients harbouring the same variant p.Ala93Thr presented with severe rippling muscle disease (PMIDs: 12666119; 15668980). Other individuals had variable presentations including isolated exercise intolerance (1), limb girdle muscular dystrophy (1), and mild proximal muscle weakness (2). One individual was asymptomatic at 49 years. In addition, 2/7 cases harboured Likely Benign variants with homozygotes reported in gnomAD (PMIDs: 9536092; 18253147). Hence, mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted, due to conflicting evidence for a BIALLELIC association. An 'expert-review' tag was added to obtain a second opinion on this proposed change.
Rhabdomyolysis and metabolic muscle disorders v6.9 CAV3 Ida Ertmanska commented on gene: CAV3: Comment on mode of inheritance: There are 7 families reported in literature with biallelic CAV3 variants and features of a metabolic muscle disorder. Only 2 patients harbouring the same variant p.Ala93Thr presented with severe rippling muscle disease (PMIDs: 12666119; 15668980). Other individuals had variable presentations including isolated exercise intolerance, limb girdle muscular dystrophy, and mild proximal muscle weakness. One individual was asymptomatic at 49 years. In addition, 2/7 cases harboured Likely Benign variants with homozygotes reported in gnomAD (PMIDs: 9536092; 18253147). Hence, mode of inheritance should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted, due to conflicting evidence for a BIALLELIC association. An 'expert-review' tag was added to obtain a second opinion on this proposed change.
Rhabdomyolysis and metabolic muscle disorders v6.9 CAV3 Ida Ertmanska Deleted their comment
Rhabdomyolysis and metabolic muscle disorders v6.9 CAV3 Ida Ertmanska edited their review of gene: CAV3: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and metabolic muscle disorders v6.9 CAV3 Ida Ertmanska Tag Q3_26_MOI was removed from gene: CAV3.
Tag watchlist_moi tag was added to gene: CAV3.
Rhabdomyolysis and metabolic muscle disorders v6.8 CAV3 Ida Ertmanska commented on gene: CAV3: Comment on mode of inheritance: There are more than 3 unrelated individuals reported in literature with biallelic CAV3 variants and a caveolinopathy, which primarily manifests in exercise intolerance and elevated CK. Proximal weakness and hypertrophy of limbs are also often reported, though the disease is often mild and slow progressing. The severity of disease does not clearly correlate with the mode of inheritance. Based on available evidence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Rhabdomyolysis and metabolic muscle disorders v6.8 CAV3 Ida Ertmanska Tag Q3_26_MOI tag was added to gene: CAV3.
Rhabdomyolysis and metabolic muscle disorders v6.8 CAV3 Ida Ertmanska Publications for gene: CAV3 were set to 15668980; 12666119; 9536092; 11251997; 16730439
Rhabdomyolysis and metabolic muscle disorders v6.7 CAV3 Ida Ertmanska Phenotypes for gene: CAV3 were changed from Myopathy, distal, Tateyama type, OMIM:614321; Rippling muscle disease, OMIM:606072 to caveolinopathy MONDO:0016146; Myopathy, distal, Tateyama type, OMIM:614321; Rippling muscle disease 2, OMIM:606072; rippling muscle disease 2, MONDO:0019947; distal myopathy, Tateyama type, MONDO:0013686
Rhabdomyolysis and metabolic muscle disorders v6.6 CAV3 Ida Ertmanska changed review comment from: PMID: 37166430 Berling et al., 2023
Report of 23 patients from 16 unrelated families (from France, Portugal, Belgium, and Algeria) with CAV3 mutations. 52% of individuals had exercise intolerance, 80% showed calf hypertrophy, and muscle rippling was seen in 65%. No cardiac or respiratory involvement noted in this cohort. CK was elevated in all patients.
2 of 23 patients were homozygous for CAV3 mutations - table claims it's patients 6 & 7:
P6 - French male, disease onset at 20yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4). No muscle weakness, only symptom was exercise intolerance.
P7 - Portugese male, NOT SYMPTOMATIC at 49 yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4).
However, text says the CAV3: c.427_431del variant was homozygous in 2 sibs with rippling muscle and calf hypertrophy from Family F (P7 and P13).

PMID: 18253147 Traverso et al., 2008
Patient 1, a 58yo female, affected by dilated cardiomyopathy and limb girdle muscular dystrophy (LGMD)-1C, showed an autosomal recessive mutation CAV3 c.233C>T, p.(T78M). Neurological examination revealed generalized hypotonia, proximal weakness and hypotrophy of the upper limbs, and proximal hypotrophy and calf hypetrophy of the lower limbs.
Variant has MAF = 0.008413 in gnomAD, including one homozygote - VUS leaning Benign.
---------------------
CAV3 is only associated with autosomal dominant disease entities in OMIM (Cardiomyopathy, familial hypertrophic, MIM:192600; Creatine phosphokinase, elevated serum, MIM:123320; Myopathy, distal, Tateyama type, MIM:614321; Rippling muscle disease 2, MIM:606072; Long QT syndrome 9, MIM:611818). The association between CAV3 and AD caveolinopathy (MONDO:0016146) was classified as Definitive in ClinGe; to: PMID: 37166430 Berling et al., 2023
Report of 23 patients from 16 unrelated families (from France, Portugal, Belgium, and Algeria) with CAV3 mutations. 52% of individuals had exercise intolerance, 80% showed calf hypertrophy, and muscle rippling was seen in 65%. No cardiac or respiratory involvement noted in this cohort. CK was elevated in all patients.
2 of 23 patients were homozygous for CAV3 mutations - table claims it's patients 6 & 7:
P6 - French male, disease onset at 20yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4). No muscle weakness, only symptom was exercise intolerance.
P7 - Portugese male, NOT SYMPTOMATIC at 49 yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4).
However, text says the CAV3: c.427_431del variant was homozygous in 2 sibs with rippling muscle and calf hypertrophy from Family F (P7 and P13).

PMID: 18253147 Traverso et al., 2008
Patient 1, a 58yo female, affected by dilated cardiomyopathy and limb girdle muscular dystrophy (LGMD)-1C, showed an autosomal recessive mutation CAV3 c.233C>T, p.(T78M). Neurological examination revealed generalized hypotonia, proximal weakness and hypotrophy of the upper limbs, and proximal hypotrophy and calf hypetrophy of the lower limbs.
Variant has MAF = 0.008413 in gnomAD, including one homozygote - VUS leaning Benign.
---------------------
CAV3 is only associated with autosomal dominant disease entities in OMIM (Cardiomyopathy, familial hypertrophic, MIM:192600; Creatine phosphokinase, elevated serum, MIM:123320; Myopathy, distal, Tateyama type, MIM:614321; Rippling muscle disease 2, MIM:606072; Long QT syndrome 9, MIM:611818). The association between CAV3 and AD caveolinopathy (MONDO:0016146) was classified as Definitive in ClinGe
Rhabdomyolysis and metabolic muscle disorders v6.6 CAV3 Ida Ertmanska edited their review of gene: CAV3: Changed publications to: 18253147, 37166430
Rhabdomyolysis and metabolic muscle disorders v6.6 CAV3 Ida Ertmanska changed review comment from: PMID: 37166430 Berling et al., 2023
Report of 23 patients from 16 unrelated families (from France, Portugal, Belgium, and Algeria) with CAV3 mutations. 52% of individuals had exercise intolerance, 80% showed calf hypertrophy, and muscle rippling was seen in 65%. No cardiac or respiratory involvement noted in this cohort. CK was elevated in all patients.
2 of 23 patients were homozygous for CAV3 mutations - table claims it's patients 6 & 7:
P6 - French male, disease onset at 20yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4). No muscle weakness, only symptom was exercise intolerance.
P7 - Portugese male, NOT SYMPTOMATIC at 49 yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4).
However, text says the CAV3: c.427_431del variant was homozygous in 2 sibs with rippling muscle and calf hypertrophy from Family F (P7 and P13).
---------------------
CAV3 is only associated with autosomal dominant disease entities in OMIM (Cardiomyopathy, familial hypertrophic, MIM:192600; Creatine phosphokinase, elevated serum, MIM:123320; Myopathy, distal, Tateyama type, MIM:614321; Rippling muscle disease 2, MIM:606072; Long QT syndrome 9, MIM:611818). The association between CAV3 and AD caveolinopathy (MONDO:0016146) was classified as Definitive in ClinGen (Muscular Dystrophies and Myopathies GCEP, Sept 2022). Resources accessed 6th Aug 2026).; to: PMID: 37166430 Berling et al., 2023
Report of 23 patients from 16 unrelated families (from France, Portugal, Belgium, and Algeria) with CAV3 mutations. 52% of individuals had exercise intolerance, 80% showed calf hypertrophy, and muscle rippling was seen in 65%. No cardiac or respiratory involvement noted in this cohort. CK was elevated in all patients.
2 of 23 patients were homozygous for CAV3 mutations - table claims it's patients 6 & 7:
P6 - French male, disease onset at 20yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4). No muscle weakness, only symptom was exercise intolerance.
P7 - Portugese male, NOT SYMPTOMATIC at 49 yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4).
However, text says the CAV3: c.427_431del variant was homozygous in 2 sibs with rippling muscle and calf hypertrophy from Family F (P7 and P13).

PMID: 18253147 Traverso et al., 2008
Patient 1, a 58yo female, affected by dilated cardiomyopathy and limb girdle muscular dystrophy (LGMD)-1C, showed an autosomal recessive mutation CAV3 c.233C>T, p.(T78M). Neurological examination revealed generalized hypotonia, proximal weakness and hypotrophy of the upper limbs, and proximal hypotrophy and calf hypetrophy of the lower limbs.
Variant has MAF = 0.008413 in gnomAD, including one homozygote - VUS leaning Benign.
---------------------
CAV3 is only associated with autosomal dominant disease entities in OMIM (Cardiomyopathy, familial hypertrophic, MIM:192600; Creatine phosphokinase, elevated serum, MIM:123320; Myopathy, distal, Tateyama type, MIM:614321; Rippling muscle disease 2, MIM:606072; Long QT syndrome 9, MIM:611818). The association between CAV3 and AD caveolinopathy (MONDO:0016146) was classified as Definitive in ClinGe
Rhabdomyolysis and metabolic muscle disorders v6.6 CAV3 Ida Ertmanska changed review comment from: PMID: 37166430 Berling et al., 2023
Report of 23 patients from 16 unrelated families (from France, Portugal, Belgium, and Algeria) with CAV3 mutations. 52% of individuals had exercise intolerance, 80% showed calf hypertrophy, and muscle rippling was seen in 65%. No cardiac or respiratory involvement noted in this cohort. CK was elevated in all patients.
2 of 23 patients were homozygous for CAV3 mutations - table claims it's patients 6 & 7:
P6 - French male, disease onset at 20yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4). No muscle weakness, only symptom was exercise intolerance.
P7 - Portugese male, NOT SYMPTOMATIC at 49 yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4).
However, text says the CAV3: c.427_431del variant was homozygous in 2 sibs with rippling muscle and calf hypertrophy from Family F (P7 and P13).; to: PMID: 37166430 Berling et al., 2023
Report of 23 patients from 16 unrelated families (from France, Portugal, Belgium, and Algeria) with CAV3 mutations. 52% of individuals had exercise intolerance, 80% showed calf hypertrophy, and muscle rippling was seen in 65%. No cardiac or respiratory involvement noted in this cohort. CK was elevated in all patients.
2 of 23 patients were homozygous for CAV3 mutations - table claims it's patients 6 & 7:
P6 - French male, disease onset at 20yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4). No muscle weakness, only symptom was exercise intolerance.
P7 - Portugese male, NOT SYMPTOMATIC at 49 yrs; homozygous for CAV3: c.427_431del, p.Ile143Glyfs*55 (not in gnomAD v4).
However, text says the CAV3: c.427_431del variant was homozygous in 2 sibs with rippling muscle and calf hypertrophy from Family F (P7 and P13).
---------------------
CAV3 is only associated with autosomal dominant disease entities in OMIM (Cardiomyopathy, familial hypertrophic, MIM:192600; Creatine phosphokinase, elevated serum, MIM:123320; Myopathy, distal, Tateyama type, MIM:614321; Rippling muscle disease 2, MIM:606072; Long QT syndrome 9, MIM:611818). The association between CAV3 and AD caveolinopathy (MONDO:0016146) was classified as Definitive in ClinGen (Muscular Dystrophies and Myopathies GCEP, Sept 2022). Resources accessed 6th Aug 2026).
Rhabdomyolysis and metabolic muscle disorders v6.6 CAV3 Ida Ertmanska reviewed gene: CAV3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37166430; Phenotypes: caveolinopathy MONDO:0016146, Myopathy, distal, Tateyama type, OMIM:614321, Rippling muscle disease 2, OMIM:606072, rippling muscle disease 2, MONDO:0019947, distal myopathy, Tateyama type, MONDO:0013686; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v2.5 CAV3 Arina Puzriakova Tag Q3_21_MOI was removed from gene: CAV3.
Rhabdomyolysis and metabolic muscle disorders v2.5 CAV3 Arina Puzriakova commented on gene: CAV3
Rhabdomyolysis and metabolic muscle disorders v2.4 CAV3 Arina Puzriakova Source NHS GMS was added to CAV3.
Mode of inheritance for gene CAV3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rhabdomyolysis and metabolic muscle disorders v1.57 CAV3 Ivone Leong Publications for gene: CAV3 were set to
Rhabdomyolysis and metabolic muscle disorders v1.56 CAV3 Ivone Leong Tag Q3_21_MOI tag was added to gene: CAV3.
Rhabdomyolysis and metabolic muscle disorders v1.56 CAV3 Ivone Leong edited their review of gene: CAV3: Added comment: MOI should be changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown".

PMID: 9536092, reported one patient with homozygous G56S. The patient was the only member of the family to be affected by disease (proximal muscle weakness in the first decade of life). The variant was not found in 200 controls. The patient's skeletal muscle biopsy looked normal and expression of dystrophin, sarcoglycans and caveolin-3 was normal. This variant was later reclassified as a VUS as PMID:11251997 identified 2 Brazilian patients with LGMD with heterozygous G55S. Both patients had onset in adulthood, calf hypertrophy, elevated creatine kinase, and difficulty walking. Muscle protein analyses from both patients were normal. Screening 200 normal controls showed 4 controls also had this variant.
In OMIM: "Hamosh (2018) found that the G55S variant was present in heterozygous state in 3,142 of 277,064 alleles and in 184 homozygotes in the gnomAD database (January 24, 2018), calling into question the pathogenicity of the variant."

PMID: 12666119, reported an Italian patient with severe rippling muscle disease (A92T) who was AR. Actually A93T.

PMID: 15668980, the same authors of PMID: 12666119 reported 1 family with 2 affected sibs who have AR rippling muscle disease (same variant as above A92T). Unaffected parents were both heterozygous for the variant. The authors note that the parents were not known to be consanguineous but they are from the same small village in Germany. The authors also did a haplotype analysis and showed that this variant arose separately from the Italian case, suggesting that A92 might be a mutation hot spot. According to ClinVar, this variant has conflicting interpretations of pathogenicity (https://www.ncbi.nlm.nih.gov/clinvar/variation/8285/).

PMID: 16730439, reports on 1 patient (AR) with mild proximal muscle weakness of the lower limbs. No other family members were available for further analysis. Patient is homozygous for a splice variant (IVS1+2T>C).

While there are cases of biallelic variants causing disease there are currently no new cases reporting of this (newest report was in 2006). There is currently not enough evidence to support biallelic cause of disease, I suggest changing the MOI to Monoallelic until more evidence is available.; Changed publications to: 15668980, 12666119, 9536092, 11251997, 16730439; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rhabdomyolysis and metabolic muscle disorders v1.48 CAV3 Ivone Leong Added comment: Comment on phenotypes: Previously:
Muscular dystrophy, limb-girdle, type IC 607801;Myopathy, distal, Tateyama type 614321;Rippling muscle disease 606072
Rhabdomyolysis and metabolic muscle disorders v1.48 CAV3 Ivone Leong Phenotypes for gene: CAV3 were changed from Muscular dystrophy, limb-girdle, type IC 607801; Myopathy, distal, Tateyama type 614321; Rippling muscle disease 606072 to Myopathy, distal, Tateyama type, OMIM:614321; Rippling muscle disease, OMIM:606072
Rhabdomyolysis and metabolic muscle disorders CAV3 Sarah Leigh marked CAV3 as ready
Rhabdomyolysis and metabolic muscle disorders CAV3 Sarah Leigh commented on CAV3
Rhabdomyolysis and metabolic muscle disorders CAV3 Ros Quinlivan reviewed CAV3