Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486600 | SCV000568283 | uncertain significance | not provided | 2016-11-22 | criteria provided, single submitter | clinical testing | The P103L variant was previously reported as a heterozygous variant in an individual with limb-girdle muscular dystrophy, however detailed clinical information was not provided and only the CAPN3 gene was evaluated (Piluso et al., 2005). It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P103L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals, and missense variants in nearby residues (R101K; P102S) have been reported in the Human Gene Mutation Database in association with limb-girdle muscular dystrophy (Stenson et al., 2014). However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Invitae | RCV001350006 | SCV001544378 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 103 of the CAPN3 protein (p.Pro103Leu). This variant is present in population databases (rs148538711, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of autosomal dominant limb-girdle muscular dystrophy (PMID: 16141003). ClinVar contains an entry for this variant (Variation ID: 420000). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
Natera, |
RCV001350006 | SCV002094438 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2020-02-14 | no assertion criteria provided | clinical testing |