ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.338T>C (p.Ile113Thr) (rs747026964)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000440617 SCV000335003 uncertain significance not provided 2018-07-03 criteria provided, single submitter clinical testing
GeneDx RCV000440617 SCV000533388 likely pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the CAPN3 gene. The I113T variant has been previously reported in a patient with LGMD2A who harbored an additional CAPN3 variant (Nilsson et al., 2014). The I113T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The I113T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Counsyl RCV000675143 SCV000800733 uncertain significance Limb-girdle muscular dystrophy, type 2A 2017-09-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000675143 SCV000914667 uncertain significance Limb-girdle muscular dystrophy, type 2A 2018-01-29 criteria provided, single submitter clinical testing The CAPN3 c.338T>C (p.Ile113Thr) variant has been reported in a compound heterozygous state with a second missense variant in one patient with limb-girdle muscular dystrophy type 2A (LGMD2A) (Nilsson et al. 2014). The p.Ile113Thr is reported at a frequency of 0.000213 in the European (non-Finnish) population from the Genome Aggregation Database. The evidence for this variant is limited. The p.Ile113Thr variant is therefore considered to be of unknown clinical significance but suspicious for pathogenicity for calpainopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Baylor Genetics RCV000675143 SCV001529404 uncertain significance Limb-girdle muscular dystrophy, type 2A 2018-05-03 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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