Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV004799591 | SCV001468803 | uncertain significance | Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies | 2019-09-13 | criteria provided, single submitter | clinical testing | The inherited c.616G>C (p.Val206Leu) variant identified in the INTS1 gene substitutes a completely conserved Valine for Leucine at amino acid 206/2191 (coding exon 5/48). This variant is found with low frequency in gnomAD (1 heterozygote, 0 homozygotes; allele frequency: 4.03e-6), and is absent from ExAC, suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms do not agree on the effect of this variant, as it is predicted both Neutral (Provean; score: -1.74) and Damaging (SIFT; score: 0.019) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literauture. Given the lack of compelling evidence supporting its pathogenicity, the c.616G>C (p.Val206Leu) variant identified in the INTS1 gene is reported here as a Variant of Uncertain Significiance. |
| Ambry Genetics | RCV005348407 | SCV006014445 | uncertain significance | Inborn genetic diseases | 2025-01-24 | criteria provided, single submitter | clinical testing | The c.616G>C (p.V206L) alteration is located in exon 5 (coding exon 4) of the INTS1 gene. This alteration results from a G to C substitution at nucleotide position 616, causing the valine (V) at amino acid position 206 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |