Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000815183 | SCV000955631 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 635 of the LRSAM1 protein (p.Ile635Met). This variant is present in population databases (rs369161790, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 658368). 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 LRSAM1 protein function with a negative predictive value of 80%. 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 | RCV002406851 | SCV002722668 | uncertain significance | Inborn genetic diseases | 2020-08-05 | criteria provided, single submitter | clinical testing | The p.I635M variant (also known as c.1905C>G), located in coding exon 22 of the LRSAM1 gene, results from a C to G substitution at nucleotide position 1905. The isoleucine at codon 635 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |