Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000213867 | SCV000279958 | uncertain significance | not provided | 2016-03-15 | criteria provided, single submitter | clinical testing | The V626G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project and was not observed with any significant frequency in the 1000 Genomes Project. The V626G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. Additionally, 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. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000649913 | SCV000771749 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 626 of the LRSAM1 protein (p.Val626Gly). This variant is present in population databases (rs574202204, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of LRSAM1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 234883). 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. 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 | RCV002408941 | SCV002721117 | uncertain significance | Inborn genetic diseases | 2022-02-28 | criteria provided, single submitter | clinical testing | The p.V626G variant (also known as c.1877T>G), located in coding exon 22 of the LRSAM1 gene, results from a T to G substitution at nucleotide position 1877. The valine at codon 626 is replaced by glycine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |