Submissions for variant NM_001379500.1(COL18A1):c.1187_1200dup (p.Pro401fs)

gnomAD frequency: 0.00001  dbSNP: rs768663340

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001944604	SCV002137126	pathogenic	not provided	2023-07-07	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs768663340, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Pro401Glyfs*36) in the COL18A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL18A1 are known to be pathogenic (PMID: 12415512, 25456301). This premature translational stop signal has been observed in individual(s) with Knobloch syndrome (PMID: 31415705). ClinVar contains an entry for this variant (Variation ID: 1366287). For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV002246563	SCV002518732	pathogenic	Knobloch syndrome	2022-05-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001944604	SCV002544685	pathogenic	not provided	2022-06-01	criteria provided, single submitter	clinical testing	COL18A1: PVS1, PM2
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV003136227	SCV003807406	pathogenic	Knobloch syndrome 1	2022-08-04	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 very strong, PS4 supporting, PM2 moderated