Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_000261.2:c.1121G>T

CA343724639

Gene: MYOC
Condition: primary open angle glaucoma
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0e4ca6b6-e46a-473e-8714-7c8602e45f45
Approved on: 2023-04-04
Published on: 2023-04-04

HGVS expressions

NM_000261.2:c.1121G>T
NC_000001.11:g.171636319C>A
CM000663.2:g.171636319C>A
NC_000001.10:g.171605459C>A
CM000663.1:g.171605459C>A
NC_000001.9:g.169872082C>A
NG_008859.1:g.21315G>T
ENST00000037502.11:c.1121G>T
ENST00000637303.1:c.235-2311C>A
ENST00000638471.1:c.*459G>T
ENST00000037502.10:c.1121G>T
ENST00000614688.1:c.*85G>T
NM_000261.1:c.1121G>T

Uncertain Significance

Met criteria codes 3
PM2_Supporting PP3 PS4_Supporting
Not Met criteria codes 12
BS3 BS1 BP7 BP4 PM6 PM5 PM4 PS2 PS1 PS3 PP1 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Glaucoma VCEP
The c.1121G>T variant in MYOC is a missense variant predicted to cause substitution of Glycine by Valine at amino acid 374 (p.Gly374Val). 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 = 0.904, 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. 2 probands with primary open angle glaucoma have been reported carrying this variant (PMID: 21552496), which met PS4_Supporting (≥ 2 probands). 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 primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): PP3, PS4_Supporting, PM2_Supporting.
Met criteria codes
PM2_Supporting
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.
PP3
The REVEL score = 0.904, which met the ≥ 0.7 threshold for PP3, predicting a damaging effect on MYOC function.
PS4_Supporting
2 probands with POAG have been reported carrying this variant (PMID: 21552496), which met PS4_Supporting (≥ 2 probands).
Not Met criteria codes
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 a synonymous or non-coding variant.
BP4
This criterion was not met as PP3 has been met.
PM6
This variant has not been identified de novo.
PM5
No other missense variants at this amino acid residue have been identified.
PM4
This variant does not cause a protein length change.
PS2
This variant has not been identified de novo.
PS1
An established pathogenic variant causing this same amino acid change has not been identified.
PS3
No functional evidence has been found for this variant.
PP1
No segregations have been reported for this variant.
BA1
This criterion was not met as PM2_Supporting has been met.
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