ClinVar Miner

Submissions for variant NM_012210.4(TRIM32):c.458_465del (p.Leu153fs)

dbSNP: rs749696299
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001248699 SCV001422205 pathogenic Bardet-Biedl syndrome 2023-07-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu153Serfs*27) in the TRIM32 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 501 amino acid(s) of the TRIM32 protein. This variant is present in population databases (rs749696299, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TRIM32-related conditions. ClinVar contains an entry for this variant (Variation ID: 972625). This variant disrupts a region of the TRIM32 protein in which other variant(s) (p.Met370Cysfs*10) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002491850 SCV002813845 likely pathogenic Sarcotubular myopathy; Bardet-Biedl syndrome 11 2021-11-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155382 SCV003844342 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy 2023-02-04 criteria provided, single submitter clinical testing Variant summary: TRIM32 c.458_465delTAACTCGT (p.Leu153SerfsX27) 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. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.691del [p.Ala231fs], c.1108del [p.Met370fs]). The variant allele was found at a frequency of 2e-05 in 251184 control chromosomes (gnomAD). To our knowledge, no occurrence of c.458_465delTAACTCGT in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and one as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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