Submissions for variant NM_001371623.1(TCOF1):c.378+1G>A

dbSNP: rs1581064385

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000792464	SCV000931765	likely pathogenic	Treacher Collins syndrome 1	2018-11-05	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 4 of the TCOF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TCOF1-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TCOF1 are known to be pathogenic (PMID: 8894686, 22317976). 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.
PreventionGenetics, part of Exact Sciences	RCV004723183	SCV005336568	likely pathogenic	TCOF1-related disorder	2024-08-22	no assertion criteria provided	clinical testing	The TCOF1 c.378+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Variants that disrupt the consensus splice donor site in TCOF1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.