Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001321962 | SCV001512814 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2020-08-27 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 variant has not been reported in the literature in individuals with LRSAM1-related conditions. This variant is present in population databases (rs752596738, ExAC 0.005%). This sequence change replaces arginine with tryptophan at codon 8 of the LRSAM1 protein (p.Arg8Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. |
| Ambry Genetics | RCV002447364 | SCV002732358 | uncertain significance | Inborn genetic diseases | 2020-03-18 | criteria provided, single submitter | clinical testing | The p.R8W variant (also known as c.22C>T), located in coding exon 1 of the LRSAM1 gene, results from a C to T substitution at nucleotide position 22. The arginine at codon 8 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well 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. |