Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001220288 | SCV001392268 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2019-05-08 | criteria provided, single submitter | clinical testing | 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. This variant has not been reported in the literature in individuals with LRSAM1-related conditions. This variant is present in population databases (rs749204843, ExAC 0.02%). This sequence change replaces proline with alanine at codon 665 of the LRSAM1 protein (p.Pro665Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. |