Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002651638 | SCV003525091 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 111 of the VHL protein (p.Ser111Cys). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. A different variant (c.331A>T) giving rise to the same protein effect has been determined to be pathogenic (PMID: 12202531, 12807974). This suggests that this variant is also likely to be causative of disease. This variant is also known as 543–544 CA→TT. ClinVar contains an entry for this variant (Variation ID: 2203305). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Ser111 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728151, 9829911, 10761708, 14722919, 25562111, 25867206, 27527340). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |