Submissions for variant NM_000090.4(COL3A1):c.4011+1G>T

dbSNP: rs112532745

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000697146	SCV000825742	pathogenic	Ehlers-Danlos syndrome, type 4	2018-07-16	criteria provided, single submitter	clinical testing	A different variant affecting this nucleotide (c.4011+1G>A) has been determined to be pathogenic (PMID: 25758994). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. 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. This variant has not been reported in the literature in individuals with COL3A1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 49 of the COL3A1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL3A1 are known to be pathogenic (PMID: 24922459). For these reasons, this variant has been classified as Pathogenic.