ClinVar Miner

Submissions for variant NM_152263.4(TPM3):c.706-2dup

dbSNP: rs1085307588
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489009 SCV000576783 uncertain significance not specified 2017-04-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TPM3 gene. The c.706-2dupA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.706-2dupA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.706-2dupA does not impact 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 variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001324618 SCV001515578 uncertain significance Congenital myopathy 4B, autosomal recessive; Congenital myopathy with fiber type disproportion 2020-01-21 criteria provided, single submitter clinical testing 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. This variant has not been reported in the literature in individuals with TPM3-related conditions. ClinVar contains an entry for this variant (Variation ID: 426365). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 7 of the TPM3 gene. It does not directly change the encoded amino acid sequence of the TPM3 protein, but it affects a nucleotide within the consensus splice site of the intron.

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