Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002280342 | SCV002568389 | uncertain significance | Glaucoma 1, open angle, E | 2022-08-28 | reviewed by expert panel | curation | The c.38C>T variant in MYOC is a missense variant predicted to cause substitution of Proline by Leucine at amino acid 13 (p.Pro13Leu). This variant was not found in any population of gnomAD (v2.1.1), meeting the <= 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The REVEL score = 0.278, which was neither above nor below the thresholds for PP3 (>= 0.7) or BP4 (<= 0.15), predicting a damaging or benign impact on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. No segregations have been reported in individuals carrying this variant and no other MYOC variant. Only 1 proband with POAG had been reported (PMID: 18776955), but he also carried the variant of uncertain significance p.Gln337ArgfsTer9 and therefore was not counted. In summary, this variant met the criteria to receive a score of 1 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PM2_Supporting. |