Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000492975 | SCV000581867 | uncertain significance | not specified | 2017-04-28 | criteria provided, single submitter | clinical testing | The c.2416_2417dupAT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.2416_2417dupAT variant causes a frameshift starting with codon Isoleucine 807, changes this amino acid to a Serine residue and creates a premature Stop codon at position 77 of the new reading frame, denoted p.Ile807SerfsX77. However, this variant is not predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. |
Invitae | RCV001043580 | SCV001207333 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2022-07-19 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the C-terminus of the CAPN3 protein. Other variant(s) that disrupt this region (p.Trp814*) have been observed in individuals with CAPN3-related conditions (PMID: 17994539). This suggests that this may be a clinically significant region of the protein. ClinVar contains an entry for this variant (Variation ID: 429326). This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile807Serfs*77) in the CAPN3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 15 amino acid(s) of the CAPN3 protein. |