Submissions for variant NM_000494.4(COL17A1):c.3277+1G>A

gnomAD frequency: 0.00010  dbSNP: rs199527325

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000729478	SCV000857145	likely pathogenic	not provided	2017-09-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000729478	SCV004276879	likely pathogenic	not provided	2024-01-27	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 47 of the COL17A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL17A1 are known to be pathogenic (PMID: 16473856, 17344927, 20301304, 21357940, 24319098). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with COL17A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 594239). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Leeds Amelogenesis Imperfecta Research Group, University of Leeds	RCV003314641	SCV004012854	pathogenic	Amelogenesis imperfecta type 1A	2023-07-12	no assertion criteria provided	research
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV003333755	SCV004041726	likely pathogenic	Epidermolysis bullosa, junctional 4, intermediate	2023-10-09	no assertion criteria provided	clinical testing