The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: MYOC vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000261.2:c.11T>C

CA343720226

1703220 (ClinVar)

Gene: MYOC (HGNC:4653)
Condition: open-angle glaucoma (MONDO:0005338)
Inheritance Mode: Autosomal dominant inheritance
UUID: ebb20c76-41a8-4819-8df4-fcf9d17e3b22
Approved on: 2025-11-13
Published on: 2025-11-12

HGVS expressions

NM_000261.2:c.11T>C
NC_000001.11:g.171652601A>G
CM000663.2:g.171652601A>G
NC_000001.10:g.171621741A>G
CM000663.1:g.171621741A>G
NC_000001.9:g.169888364A>G
NG_008859.1:g.5033T>C
ENST00000037502.11:c.11T>C
ENST00000638471.1:c.11T>C
ENST00000037502.10:c.11T>C
ENST00000614688.1:c.11T>C
NM_000261.1:c.11T>C
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Uncertain Significance

Met criteria codes 3
BP4 PM2_Supporting PS4_Supporting
Not Met criteria codes 11
BA1 BS3 BS1 BP7 PS2 PS1 PS3 PP1 PP3 PM5 PM4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MYOC Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.11T>C variant in MYOC is a missense variant predicted to cause substitution of Phenylalanine by Serine at amino acid 4 (p.Phe4Ser). The highest minor allele frequency of this variant was in the European (non-Finnish) genetic ancestry group of gnomAD (v4.1.0) = 0.000002542 (3 alleles out of 1,180,040), which met the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles. The REVEL score = 0.068, which was within the 0.017-0.183 range for BP4_Moderate, suggesting that the variant does not impact MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Only 1 segregation had been reported for primary open angle glaucoma (POAG) (Charlesworth, J. 2006 PhD Thesis), not meeting the ≥ 3 segregations required for PP1. 2 probands with POAG have been reported carrying this variant (PMID: 10196380), which met PS4_Supporting (≥ 2 probands). In summary, this variant met the criteria to receive a score of 0 and to be classified as a variant of uncertain significance (uncertain significance classification range -1 to 5, adapted from PMID: 32720330) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v2.0.0, 5 Dec 2024): BP4_Moderate, PM2_Supporting, PS4_Supporting.
Met criteria codes
BP4
Moderate level: The REVEL score = 0.068, which was within the 0.017-0.183 range for BP4_Moderate, suggesting that the variant does not impact MYOC function.
PM2_Supporting
The highest minor allele frequency of this variant was in the European (non-Finnish) genetic ancestry group of gnomAD (v4.1.0) = 0.000002542 (3 alleles out of 1,180,040), which met the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles.
PS4_Supporting
2 probands with POAG have been reported carrying this variant (PMID: 10196380), which met PS4_Supporting (≥ 2 probands).
Not Met criteria codes
BA1
This criterion was not met as PM2_Supporting has been met.
BS3
No functional evidence has been found for this variant.
BS1
This criterion was not met as PM2_Supporting has been met.
BP7
This is not an intronic, synonymous or non-coding variant.
PS2
This variant has not been identified de novo.
PS1
An established LP or P variant causing this same amino acid change has not been identified.
PS3
No functional evidence has been found for this variant.
PP1
Only 1 segregation had been reported for primary open angle glaucoma (Charlesworth, J. 2006 PhD Thesis), not meeting the ≥ 3 segregations required for PP1.
PP3
This criterion was not met as BP4 has been met.
PM5
No other LP or P missense variants at this amino acid residue have been identified.
PM4
This variant does not cause a protein length change.
Curation History
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