Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001035277 | SCV001198600 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2020-03-03 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 4 of the SH3TC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs145670786, ExAC 0.004%). This variant has been observed in individual(s) with hereditary neuropathy (Invitae). 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 SH3TC2 are known to be pathogenic (PMID: 20220177, 27068304). For these reasons, this variant has been classified as Pathogenic. |
Genesis Genome Database | RCV000857159 | SCV000999740 | uncertain significance | Distal spinal muscular atrophy | 2019-08-14 | no assertion criteria provided | research |