Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003336597 | SCV004046616 | uncertain significance | Timothy syndrome; Long qt syndrome 8; Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures | 2022-11-28 | criteria provided, single submitter | clinical testing | The c.6404T>A p.(Val2135Asp) variant in the CACNA1C gene has not previously been reported in the literature or public variant repositories (ClinVar and LOVD), and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.6404T>A variant in CACNA1C is located in exon 47 of this 47-exon gene, and predicted to replace an evolutionarily conserved valine amino acid with aspartic acid at position 2135 of the encoded protein. In silico predictions are not in favor of damaging effect forp.(Val2135Asp) [(CADD v1.6 = 24.5, REVEL = 0.182)]; however, there are no functional studies to support or refute these predictions. Based on available evidence this c.6404T>A p.(Val2135Asp) variant identified in CACNA1C is classified as a Variant of Uncertain Significance. |