Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000200652 | SCV000253933 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2019-05-21 | criteria provided, single submitter | clinical testing | This sequence change affects codon 93 of the SH3TC2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SH3TC2 protein. This variant also falls at the last nucleotide of exon 3 of the SH3TC2 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs776221160, ExAC 0.003%). This variant has been observed on the opposite chromosome (in trans) from or in combination with a pathogenic variant in individuals affected with Charcot-Marie-Tooth disease type 4 (PMID: 21291453, 27231023). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 216120). Experimental studies have shown that this sequence change interferes with splicing of intron 3 in vitro (PMID: 22950825). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). For these reasons, this variant has been classified as Pathogenic. |
Inherited Neuropathy Consortium | RCV000789577 | SCV000928933 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |