Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000653914 | SCV000775804 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2019-05-29 | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in several individuals with a personal or family history of LMNA-related conditions (PMID: 27884249). In addition, this variant was observed in an individual with cardiomyopathy and skeletal muscle weakness (Invitae), the individual's parents reportedly did not not carry the p.Tyr81His variant suggesting that it arose de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 81 of the LMNA protein (p.Tyr81His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. 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. |
| Athena Diagnostics | RCV001289082 | SCV001476661 | likely pathogenic | not provided | 2020-01-14 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality. Predicted to have a damaging effect on the protein. One de novo case with parental identity confirmed. |