Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521297 | SCV000618155 | uncertain significance | not provided | 2017-05-12 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ITGA7 gene. The V561M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V561M variant is observed in 66/126632 (0.05%) alleles from individuals of European background, in large population cohorts (Lek et al., 2016). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with ITGA7-related disorders (Stenson et al., 2014); however, the V561M substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000558797 | SCV000648308 | uncertain significance | Congenital muscular dystrophy due to integrin alpha-7 deficiency | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 561 of the ITGA7 protein (p.Val561Met). This variant is present in population databases (rs150089409, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ITGA7-related conditions. ClinVar contains an entry for this variant (Variation ID: 309787). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ITGA7 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 | RCV004021551 | SCV003699289 | uncertain significance | not specified | 2021-09-17 | criteria provided, single submitter | clinical testing | The c.1681G>A (p.V561M) alteration is located in exon 12 (coding exon 12) of the ITGA7 gene. This alteration results from a G to A substitution at nucleotide position 1681, causing the valine (V) at amino acid position 561 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV000558797 | SCV003811458 | uncertain significance | Congenital muscular dystrophy due to integrin alpha-7 deficiency | 2023-09-04 | criteria provided, single submitter | clinical testing |