Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001371898 | SCV001568482 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2020-09-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 523 of the LRSAM1 protein (p.Gln523Glu). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LRSAM1-related conditions. 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 tolerated, 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. |
| Ambry Genetics | RCV002550140 | SCV003596400 | uncertain significance | Inborn genetic diseases | 2021-12-20 | criteria provided, single submitter | clinical testing | The c.1567C>G (p.Q523E) alteration is located in exon 20 (coding exon 19) of the LRSAM1 gene. This alteration results from a C to G substitution at nucleotide position 1567, causing the glutamine (Q) at amino acid position 523 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |