Submissions for variant NM_000261.2(MYOC):c.907C>A (p.Leu303Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Glaucoma Variant Curation Expert Panel	RCV002306273	SCV002600130	uncertain significance	Glaucoma 1, open angle, E	2022-11-09	reviewed by expert panel	curation	The c.907C>A variant in MYOC is a missense variant predicted to cause substitution of Leucine by Isoleucine at amino acid 303 (p.Leu303Ile). The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.0006817 (17 alleles out of 24,938), which did not meet the PM2_Supporting allele frequency threshold (<= 0.0001) or the BS1 allele frequency threshold (>= 0.001). The REVEL score = 0.17, which was neither above nor below the thresholds for PP3 (>= 0.7) or BP4 (<= 0.15), predicting a damaging or benign impact on MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Although a proband with primary open angle glaucoma had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant did not meet any criteria, receiving a score of 0 and a classification 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): none
Ambry Genetics	RCV003099103	SCV003757317	uncertain significance	Inborn genetic diseases	2021-07-09	criteria provided, single submitter	clinical testing	The c.907C>A (p.L303I) alteration is located in exon 3 (coding exon 3) of the MYOC gene. This alteration results from a C to A substitution at nucleotide position 907, causing the leucine (L) at amino acid position 303 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.