ClinVar Miner

Submissions for variant NM_024577.4(SH3TC2):c.3627T>A (p.Tyr1209Ter)

gnomAD frequency: 0.00001  dbSNP: rs1248359114
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001956024 SCV002226913 pathogenic Charcot-Marie-Tooth disease type 4 2023-01-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1444894). This premature translational stop signal has been observed in individual(s) with neuropathy (PMID: 25614874). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr1209*) 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003388065 SCV004099845 pathogenic Charcot-Marie-Tooth disease type 4C 2023-09-14 criteria provided, single submitter clinical testing Variant summary: SH3TC2 c.3627T>A (p.Tyr1209X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251484 control chromosomes. c.3627T>A has been reported in the literature in at least one individual referred for clinical testing due to neuropathy (DiVincenzo_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 25614874). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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