ClinVar

Description

The c.1441C>T variant in MYOC is a missense variant predicted to cause substitution of Proline by Serine at amino acid 481 (p.Pro481Ser). The highest minor allele frequency of this variant was in the East Asian population of gnomAD (v2.1.1) = 0.00005438 (1 allele out of 18,388), which met the <= 0.0001 threshold set for PM2_Supporting in a population of at least 10,000 alleles. The REVEL score = 0.684, 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. A previous study (PMID: 35196929) demonstrated conflicting results for the Pro481Ser protein, therefore, PS3 or BS3 was not applied. Only 1 proband with primary open angle glaucoma had been reported (PMID: 15534471), not meeting the >= 2 probands threshold required to meet PS4_Supporting. 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