Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV002509149 | SCV002818487 | uncertain significance | Glaucoma of childhood | 2022-12-14 | reviewed by expert panel | curation | The c.1196G>T variant in MYOC is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 399 (p.Gly399Val). The highest minor allele frequency of this variant was in the Latino/Admixed American population of gnomAD (v2.1.1) = 0.0001156 (4 alleles out of 34,592), which did not meet the PM2_Supporting allele frequency threshold (<=0.0001) or the BS1 allele frequency threshold (>= 0.001). The REVEL score = 0.968, which met the >= 0.7 threshold for PP3, predicting a damaging effect on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. 10 segregations in 1 family, with juvenile or primary open angle glaucoma (JOAG or POAG), have been reported (PMID: 11774072), which fulfilled PP1_Moderate (5-6 meioses). Although a proband with JOAG had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant met the criteria to receive a score of 3 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PP1_Moderate, PP3. |
| Labcorp Genetics |
RCV002512906 | SCV003523918 | pathogenic | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt MYOC protein function. ClinVar contains an entry for this variant (Variation ID: 7957). This missense change has been observed in individual(s) with glaucoma (PMID: 11774072). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs28936694, gnomAD 0.009%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 399 of the MYOC protein (p.Gly399Val). |
| OMIM | RCV000008420 | SCV000028628 | pathogenic | GLAUCOMA 1, OPEN ANGLE, A, DIGENIC | 2002-02-01 | no assertion criteria provided | literature only |