Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756045 | SCV000883755 | uncertain significance | not provided | 2018-01-03 | criteria provided, single submitter | clinical testing | The p.Gln1707Leu variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) identified on a single chromosome out of 30,986. The glutamine at position 1707 is highly conserved up to zebrafish considering 12 species (Alamut v2.10), and computational analyses of the effects of the p.Gln1707Leu variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, Align GVGD: Class C25). Altogether, there is not enough evidence to classify the p.Gln1707Leu variant with certainty. |
| Labcorp Genetics |
RCV001227517 | SCV001399878 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-11-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1707 of the DSP protein (p.Gln1707Leu). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 618070). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Ambry Genetics | RCV002334418 | SCV002642232 | uncertain significance | Cardiovascular phenotype | 2024-05-20 | criteria provided, single submitter | clinical testing | The p.Q1707L variant (also known as c.5120A>T), located in coding exon 23 of the DSP gene, results from an A to T substitution at nucleotide position 5120. The glutamine at codon 1707 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in a cardiovascular disease cohort (Fernandez-Falgueras A et al. PLoS One, 2024 May;19:e0297914). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| All of Us Research Program, |
RCV004807125 | SCV005428968 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-04-23 | criteria provided, single submitter | clinical testing |