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.1105T>C

CA343724711

Gene: MYOC

Condition: primary open angle glaucoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f99e041c-8dcd-4b30-a4bd-cf14e519da75

HGVS expressions

NM_000261.2:c.1105T>C

NC_000001.11:g.171636335A>G

CM000663.2:g.171636335A>G

NC_000001.10:g.171605475A>G

CM000663.1:g.171605475A>G

NC_000001.9:g.169872098A>G

NG_008859.1:g.21299T>C

ENST00000037502.11:c.1105T>C

ENST00000637303.1:c.235-2295A>G

ENST00000638471.1:c.*443T>C

ENST00000037502.10:c.1105T>C

ENST00000614688.1:c.*69T>C

NM_000261.1:c.1105T>C

Uncertain Significance

PP3 PM2_Supporting PS4_Supporting

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

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.1105T>C 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 = 0.872, 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 primary open angle glaucoma (PMIDs: 28564705, 15534471), not meeting the ≥ 3 segregations required for PP1. 2 probands with POAG have been reported carrying this variant (PMIDs: 15534471, 28564705), 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

PP3

The REVEL score = 0.872, 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.

PS4_Supporting

2 probands with POAG have been reported carrying this variant (PMIDs: 15534471, 28564705), which met PS4_Supporting (≥ 2 probands).

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.

BA1

This criterion was not met as PM2_Supporting has been met.

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.1107C>G), was not classified as likely pathogenic or pathogenic.

PS3

No functional evidence has been found for this variant.

PP1

Only 2 segregations had been reported for primary open angle glaucoma (PMIDs: 28564705, 15534471), 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.

Approved on: 2022-11-10

Published on: 2022-11-10

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.