Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000800823 | SCV000940559 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2022-11-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. 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. 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 LRSAM1 protein function. ClinVar contains an entry for this variant (Variation ID: 646525). This variant is present in population databases (rs772793971, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 530 of the LRSAM1 protein (p.Arg530Trp). |
| Ambry Genetics | RCV002397614 | SCV002706759 | uncertain significance | Inborn genetic diseases | 2021-03-28 | criteria provided, single submitter | clinical testing | The p.R530W variant (also known as c.1588C>T), located in coding exon 19 of the LRSAM1 gene, results from a C to T substitution at nucleotide position 1588. The arginine at codon 530 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant Charcot-Marie-Tooth disease; however, its contribution to the development of autosomal recessive Charcot-Marie-Tooth disease is uncertain. |