Submissions for variant NM_024577.3(SH3TC2):c.1002-5T>A (rs769711653)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000659033	SCV000293013	uncertain significance	not provided	2017-11-13	criteria provided, single submitter	clinical testing	The c.1002-5 T>A variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Multiple in-silico splice prediction models predict that c.1002-5 T>A may weaken or destroy the natural splice acceptor site in intron 8 and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000659033	SCV000780837	uncertain significance	not provided	2017-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000818193	SCV000958792	uncertain significance	Charcot-Marie-Tooth disease type 4	2018-10-29	criteria provided, single submitter	clinical testing	This sequence change falls in intron 8 of the SH3TC2 gene. It does not directly change the encoded amino acid sequence of the SH3TC2 protein. This variant is present in population databases (rs769711653, ExAC 0.009%). This variant has not been reported in the literature in individuals with SH3TC2-related disease. ClinVar contains an entry for this variant (Variation ID: 245849). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc	RCV000659033	SCV001145600	uncertain significance	not provided	2018-11-27	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173169	SCV001336249	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing