Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000398773 | SCV000434787 | benign | Pseudohypoparathyroidism type 1B | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Invitae | RCV002520026 | SCV003248338 | uncertain significance | not provided | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 215 of the STX16 protein (p.His215Leu). This variant is present in population databases (rs185111037, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with STX16-related conditions. ClinVar contains an entry for this variant (Variation ID: 339054). 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 STX16 protein function with a negative predictive value of 80%. 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 | RCV002520025 | SCV003711911 | uncertain significance | Inborn genetic diseases | 2022-12-06 | criteria provided, single submitter | clinical testing | The c.644A>T (p.H215L) alteration is located in exon 6 (coding exon 6) of the STX16 gene. This alteration results from a A to T substitution at nucleotide position 644, causing the histidine (H) at amino acid position 215 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |