Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236486 | SCV000292968 | uncertain significance | not provided | 2015-07-16 | criteria provided, single submitter | clinical testing | The R624G variant has not been published as pathogenic nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R624G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved in mammals. However, missense variants in the LRSAM1 gene have not been reported in association with neuropathy (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant. |
| Invitae | RCV001071744 | SCV001237064 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2023-07-22 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs375938990, gnomAD 0.002%). 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) performed at Invitae indicates that this missense variant is not expected to disrupt LRSAM1 protein function. ClinVar contains an entry for this variant (Variation ID: 245821). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 624 of the LRSAM1 protein (p.Arg624Gly). |
| ARUP Laboratories, |
RCV001071744 | SCV002048791 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2021-04-17 | criteria provided, single submitter | clinical testing | The LRSAM1 c.1870C>G; p.Arg624Gly variant (rs375938990), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 245821). This variant is found in the non-Finnish European population with an allele frequency of 0.0023% (3/128,926 alleles) in the Genome Aggregation Database. The arginine at codon 624 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.432). Due to limited information, the clinical significance of the p.Arg624Gly variant is uncertain at this time. |
| Ambry Genetics | RCV002411067 | SCV002722316 | uncertain significance | Inborn genetic diseases | 2020-11-24 | criteria provided, single submitter | clinical testing | The p.R624G variant (also known as c.1870C>G), located in coding exon 22 of the LRSAM1 gene, results from a C to G substitution at nucleotide position 1870. The arginine at codon 624 is replaced by glycine, 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. |