Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000197814 | SCV000255297 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2024-01-28 | criteria provided, single submitter | clinical testing | This variant, c.123_137del, results in the deletion of 5 amino acid(s) of the VHL protein (p.Ser43_Glu47del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs758049121, gnomAD 0.03%). This variant has been observed in individual(s) with von Hippel-Lindau (VHL) disease (PMID: 15300849). ClinVar contains an entry for this variant (Variation ID: 216870). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV000222096 | SCV000276096 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-09 | criteria provided, single submitter | clinical testing | The c.123_137del15 variant (also known as p.E43_P47del) is located in coding exon 1 of the VHL gene. This variant results from an in-frame AGAGTCCGGCCCGGA deletion at nucleotide positions 123 to 137. This results in the in-frame deletion of codons 43 through 47. This alteration has been previously identified in an individual from the French VHL Registry (Gallou C, et al. Hum. Mutat. 2004 Sep;24(3):215-24). However, there is an alternate in-frame methionine 54 amino acids from the primary initiation site in VHL which is reported to result in a biologically active isoform known as VHL19 (Iliopoulos O et al. Proc. Natl. Acad. Sci. U.S.A. 1998 Sep; 95(20):11661-6. Schoenfeld A et al. Proc. Natl. Acad. Sci. U.S.A. 1998 Jul; 95(15):8817-22). The amino acids impacted by the c.123_137del15 alteration are located 5' of this alternative initiation codon and as such their significance is unclear. This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000255039 | SCV000322352 | likely benign | not provided | 2021-03-12 | criteria provided, single submitter | clinical testing | In silico analysis supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 15300849) |
| Mendelics | RCV000987110 | SCV001136308 | uncertain significance | Von Hippel-Lindau syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing |