Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002007641 | SCV002260226 | uncertain significance | Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 253 of the SPATA5 protein (p.Tyr253Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs755128357, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with SPATA5-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPATA5 protein function. 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. |