Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001937277 | SCV002130278 | uncertain significance | not provided | 2025-01-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 978 of the DCHS1 protein (p.Arg978Cys). This variant is present in population databases (rs201160085, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with DCHS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1363973). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DCHS1 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. |
| Ambry Genetics | RCV004039865 | SCV004854664 | uncertain significance | Inborn genetic diseases | 2023-12-20 | criteria provided, single submitter | clinical testing | The c.2932C>T (p.R978C) alteration is located in exon 6 (coding exon 5) of the DCHS1 gene. This alteration results from a C to T substitution at nucleotide position 2932, causing the arginine (R) at amino acid position 978 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV005050426 | SCV005683705 | uncertain significance | Van Maldergem syndrome 1; Mitral valve prolapse, myxomatous 2 | 2024-05-03 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics Laboratory, |
RCV005050426 | SCV005685384 | uncertain significance | Van Maldergem syndrome 1; Mitral valve prolapse, myxomatous 2 | 2024-08-02 | criteria provided, single submitter | clinical testing | The DCHS1 c.2932C>T (p.Arg978Cys) variant was identified at a heterozygous allelic fraction of 50.2%, which may be consistent with germline origin. This variant, to our knowledge, has not been reported in the medical literature. This variant has been reported as a germline variant of uncertain significance by two submitters (ClinVar ID: 1363973). This variant is observed on 795/1,512,626 alleles in the general population (gnomAD v.4.1.0). Computational predictors suggest that the variant does not impact DCHS1 function. Due to limited information and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the DCHS1 c.2932C>T (p.Arg978Cys) variant is uncertain at this time. |