Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002441769 | SCV002749281 | uncertain significance | Cardiovascular phenotype | 2022-05-04 | criteria provided, single submitter | clinical testing | The p.P940S variant (also known as c.2818C>T), located in coding exon 22 of the DMD gene, results from a C to T substitution at nucleotide position 2818. The proline at codon 940 is replaced by serine, an amino acid with similar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.0005% (1/182865) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.0012% (1/81610) of European (non-Finnish) alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV003146572 | SCV003829471 | uncertain significance | not provided | 2019-11-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003621664 | SCV004548338 | uncertain significance | Duchenne muscular dystrophy | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 940 of the DMD protein (p.Pro940Ser). 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 DMD protein function. ClinVar contains an entry for this variant (Variation ID: 1796395). This variant has not been reported in the literature in individuals affected with DMD-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. |