Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001039402 | SCV001202932 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 611 of the LRSAM1 protein (p.Val611Met). This variant is present in population databases (rs771783337, gnomAD 0.07%). 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: 837956). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | RCV002409382 | SCV002711165 | uncertain significance | Inborn genetic diseases | 2019-09-21 | criteria provided, single submitter | clinical testing | The p.V611M variant (also known as c.1831G>A) is located in coding exon 22 of the LRSAM1 gene. The valine at codon 611 is replaced by methionine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 22. 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. |
Mayo Clinic Laboratories, |
RCV003480913 | SCV004225100 | uncertain significance | not provided | 2022-12-07 | criteria provided, single submitter | clinical testing | BP4 |