Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000261.2:c.760C>A

CA343726248

2429764 (ClinVar)

Gene: MYOC (HGNC:4653)

Condition: open-angle glaucoma (MONDO:0005338)

Inheritance Mode: Autosomal dominant inheritance

UUID: 34a2100b-b9f7-4a83-b98b-20471a046610

Approved on: 2026-01-21

Published on: 2026-01-20

HGVS expressions

NM_000261.2:c.760C>A

NC_000001.11:g.171636680G>T

CM000663.2:g.171636680G>T

NC_000001.10:g.171605820G>T

CM000663.1:g.171605820G>T

NC_000001.9:g.169872443G>T

NG_008859.1:g.20954C>A

ENST00000037502.11:c.760C>A

ENST00000637303.1:c.235-1950G>T

ENST00000638471.1:c.*98C>A

ENST00000037502.10:c.760C>A

ENST00000614688.1:c.760C>A

NM_000261.1:c.760C>A

Likely Pathogenic

PS4_Supporting PP3_Strong PM2_Supporting

PP1 BA1 PM4 PM5 BS3 BS1 PS2 PS3 PS1 BP4 BP7

Evidence Links 0

Expert Panel

Glaucoma VCEP

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.760C>A variant in MYOC is a missense variant predicted to cause substitution of Proline by Threonine at amino acid 254 (p.Pro254Thr). This variant was not found in any genetic ancestry group of gnomAD (v4.1.0), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles. The REVEL score = 0.933, which met the ≥ 0.932 threshold for PP3_Strong, predicting a damaging effect on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. 2 probands with juvenile or primary open angle glaucoma have been reported carrying this variant (PMIDs: 32830442, 33793440), which met PS4_Supporting (≥ 2 probands). In summary, this variant met the criteria to receive a score of 6 and to be classified as likely pathogenic (likely pathogenic classification range 6 to 9, adapted from PMID: 32720330) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v2.0.0, 5 Dec 2024): PP3_Strong, PS4_Supporting, PM2_Supporting.

PS4_Supporting

2 probands with JOAG or POAG have been reported carrying this variant (PMIDs: 32830442, 33793440), which met PS4_Supporting (≥ 2 probands).

PP3_Strong

The REVEL score = 0.933, which met the ≥ 0.932 threshold for PP3_Strong, predicting a damaging effect on MYOC function.

PM2_Supporting

This variant was not found in any genetic ancestry group of gnomAD (v4.1.0), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles.

PP1

No segregations have been reported for this variant.

BA1

This criterion was not met as PM2_Supporting has been met.

PM4

This variant does not cause a protein length change.

PM5

PM5 could not be applied to this variant as the other missense variants at this amino acid residue have higher Grantham scores.

BS3

No functional evidence has been found for this variant.

BS1

This criterion was not met as PM2_Supporting has been met.

PS2

This variant has not been identified de novo.

PS3

No functional evidence has been found for this variant.

PS1

An established LP or P variant causing this same amino acid change has not been identified.

BP4

This criterion was not met as PP3 has been met.

BP7

This criterion did not apply to this variant.

Curation History

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