Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000282124 | SCV000342094 | uncertain significance | not provided | 2016-05-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001039650 | SCV001203189 | uncertain significance | Qualitative or quantitative defects of dysferlin | 2022-04-21 | 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 sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2066 of the DYSF protein (p.Ala2066Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 288090). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DYSF protein function. This variant disrupts the p.Ala2066 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been observed in individuals with DYSF-related conditions (PMID: 21522182), which suggests that this may be a clinically significant amino acid residue. |