ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1722del (p.Ser575fs)

dbSNP: rs1366387924
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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.
GenomeConnect, ClinGen 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.

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