Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003582831 | SCV004311443 | uncertain significance | Primary ciliary dyskinesia 28 | 2022-12-22 | 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. 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 SPAG1 protein function. This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 181 of the SPAG1 protein (p.Thr181Met). |
| Ambry Genetics | RCV004823169 | SCV005507358 | uncertain significance | Primary ciliary dyskinesia | 2024-08-11 | criteria provided, single submitter | clinical testing | The c.542C>T (p.T181M) alteration is located in exon 6 (coding exon 5) of the SPAG1 gene. This alteration results from a C to T substitution at nucleotide position 542, causing the threonine (T) at amino acid position 181 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |