ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1746-20C>G (rs201892814)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078089 SCV000109927 likely benign not specified 2016-11-23 criteria provided, single submitter clinical testing
GeneDx RCV000078089 SCV000568286 uncertain significance not specified 2017-10-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CAPN3 gene. The c.1746-20 C>G variant has been reported multiple times in association with LGMD2A (Aartsma-Rus et al., 2006; Balci et al., 2006; Guglieri et al., 2008; Piluso et al., 2005). However, conflicting evidence has been reported regarding the effect of this variant on splicing and RNA expression. Specifically, Krahn et al. (2007) reported no splicing abnormalities by cDNA analysis of a muscle biopsy from a patient with c.1746-20 C>G and a pathogenic variant, but Western blot analysis showed reduced protein expression. However, Nascimbeni et al. (2010) reported that c.1746-20 C>G altered both RNA splicing by cDNA analysis and protein expression by Western blot in an individual who was compound heterozygous for this variant and a pathogenic variant. The NHLBI Exome Sequencing Project reports c.1746-20 C>G was observed in 33/8598 (0.4%) alleles from individuals of European background, and the 1000 Genomes Project reports it was not observed with any significant frequency. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000559180 SCV000645480 benign Limb-girdle muscular dystrophy, type 2A 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585323 SCV000692807 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626578 SCV000747279 pathogenic Elevated serum creatine phosphokinase; Migraine; Difficulty walking; Positive Romberg sign; Paresthesia; EMG: neuropathic changes; Progressive spinal muscular atrophy; Absent muscle fiber calpain-3 2017-01-01 criteria provided, single submitter clinical testing
Counsyl RCV000559180 SCV000796481 uncertain significance Limb-girdle muscular dystrophy, type 2A 2017-12-18 criteria provided, single submitter clinical testing

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