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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000261.2:c.1107C>G

CA343724698

Gene: MYOC

Condition: juvenile open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 138a995e-bfb0-4d14-9a1c-5f4353fb81d0

HGVS expressions

NM_000261.2:c.1107C>G

NC_000001.11:g.171636333G>C

CM000663.2:g.171636333G>C

NC_000001.10:g.171605473G>C

CM000663.1:g.171605473G>C

NC_000001.9:g.169872096G>C

NG_008859.1:g.21301C>G

ENST00000037502.11:c.1107C>G

ENST00000637303.1:c.235-2297G>C

ENST00000638471.1:c.*445C>G

ENST00000037502.10:c.1107C>G

ENST00000614688.1:c.*71C>G

NM_000261.1:c.1107C>G

Uncertain Significance

PP3 PM2_Supporting

PS3 PS4 PS2 PS1 BP4 BP7 BA1 PP1 PM5 PM4 PM6 BS3 BS1

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1107C>G variant in MYOC is a missense variant predicted to cause substitution of Phenylalanine by Leucine at amino acid 369 (p.Phe369Leu). 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 = 0.825, 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. Only 2 segregations had been reported for juvenile open angle glaucoma (JOAG, PMID: 35389460), not meeting the ≥ 3 segregations required for PP1. Only 1 proband with JOAG had been reported (PMID: 35389460), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. In summary, this variant met the criteria to receive a score of 2 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): PP3, PM2_Supporting

PP3

The REVEL score = 0.825, which met the ≥ 0.7 threshold for PP3, predicting a damaging effect on MYOC function.

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.

PS3

No functional evidence has been found for this variant.

PS4

Only 1 proband with JOAG had been reported (PMID: 35389460), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.

PS2

This variant has not been identified de novo.

PS1

PS1 could not be applied to this variant as the same amino acid change (p.Phe369Leu), resulting from a different nucleotide change (c.1105T>C), was not classified as likely pathogenic or pathogenic.

BP4

This criterion was not met as PP3 has been met.

BP7

This is not a synonymous or non-coding variant.

BA1

This criterion was not met as PM2_Supporting has been met.

PP1

Only 2 segregations had been reported for juvenile open angle glaucoma (PMID: 35389460), not meeting the ≥ 3 segregations required for PP1.

PM5

No other missense variants at this amino acid residue have been identified.

PM4

This variant does not cause a protein length change.

PM6

This variant has not been identified de novo.

BS3

No functional evidence has been found for this variant.

BS1

This criterion was not met as PM2_Supporting has been met.

Approved on: 2023-04-04

Published on: 2023-04-04

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