Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000528608 | SCV000652022 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2022-07-12 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 472793). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 540 of the LRSAM1 protein (p.Ser540Ile). |
Molecular Genetics Laboratory, |
RCV001173638 | SCV001336740 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Gene |
RCV001755885 | SCV002007726 | uncertain significance | not provided | 2021-01-22 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32376792) |
Ambry Genetics | RCV002395451 | SCV002703219 | uncertain significance | Inborn genetic diseases | 2020-01-13 | criteria provided, single submitter | clinical testing | The p.S540I variant (also known as c.1619G>T), located in coding exon 20 of the LRSAM1 gene, results from a G to T substitution at nucleotide position 1619. The serine at codon 540 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |