Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001065997 | SCV001230990 | uncertain significance | Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 867 of the ANO5 protein (p.Arg867Ile). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ANO5-related conditions. ClinVar contains an entry for this variant (Variation ID: 859806). 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 expected to disrupt ANO5 protein function. 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. |
Ambry Genetics | RCV003283951 | SCV003973917 | uncertain significance | Inborn genetic diseases | 2023-04-18 | criteria provided, single submitter | clinical testing | The c.2600G>T (p.R867I) alteration is located in exon 22 (coding exon 22) of the ANO5 gene. This alteration results from a G to T substitution at nucleotide position 2600, causing the arginine (R) at amino acid position 867 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |