Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003581566 | SCV004292876 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2023-03-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu832Hisfs*8) in the SH3TC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SH3TC2 are known to be pathogenic (PMID: 20220177, 27068304). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 14574644). ClinVar contains an entry for this variant (Variation ID: 21694). For these reasons, this variant has been classified as Pathogenic. |
| Foundation for Research in Genetics and Endocrinology, |
RCV000020892 | SCV005397920 | pathogenic | Charcot-Marie-Tooth disease type 4C | 2024-10-15 | criteria provided, single submitter | clinical testing | A homozygous 2 base pair deletion in exon 11 of the SH3TC2 gene that results in a frameshift and premature truncation of the protein 8 amino acids downstream to codon 832 was detected. The observed variant has previously been reported in patients state affected with Charcot-Marie-Tooth disease. This variant has not been reported in the 1000 genomes and gnomAD (v2.1) databases and has a minor allele frequency of 0.00066%, 0.00076% and 0.00623% in the gnomAD (v3.1), topmed and our internal databases respectively. The in silico predictions# of the variant is damaging by MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as variant of uncertain significance. |
| Gene |
RCV000020892 | SCV000041488 | not provided | Charcot-Marie-Tooth disease type 4C | no assertion provided | literature only |