ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1722del (p.Ser575fs) (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 Limb-girdle muscular dystrophy, type 2A 2018-08-08 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another CAPN3 variant in individuals affected with limb-girdle muscular dystrophy type 2A (PMID: 15351423, 25135358). ClinVar contains an entry for this variant (Variation ID: 503683). Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). For these reasons, this variant has been classified as Pathogenic.
GenomeConnect, ClinGen RCV000796843 SCV000986702 not provided 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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