Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000599177 | SCV000709911 | likely pathogenic | not provided | 2017-12-14 | criteria provided, single submitter | clinical testing | The c.1722delC variant in the CAPN3 gene has been previously reported in limb-girdle muscular dystrophy type 2A, in an affected individual who was also reported with a second CAPN3 variant (Chrobáková et al., 2004). The c.1722delC variant causes a frameshift starting with codon Serine 575, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 20 of the new reading frame, denoted Ser575LeufsX20. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1722delC variant is not observed in the homozygous state or at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1722delC as a likely pathogenic variant. |
Invitae | RCV000796843 | SCV000936373 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser575Leufs*20) in the CAPN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with limb-girdle muscular dystrophy type 2A (PMID: 15351423, 25135358). ClinVar contains an entry for this variant (Variation ID: 503683). For these reasons, this variant has been classified as Pathogenic. |
Genome |
RCV000796843 | SCV000986702 | not provided | Autosomal recessive limb-girdle muscular dystrophy type 2A | no assertion provided | phenotyping only | Variant interpretted as Likely pathogenic and reported on 12/15/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |