ClinVar Miner

Submissions for variant NM_145261.4(DNAJC19):c.130-1G>C

gnomAD frequency: 0.00001  dbSNP: rs137854888
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000002028 SCV000940260 pathogenic 3-methylglutaconic aciduria type 5 2022-10-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change affects an acceptor splice site in intron 3 of the DNAJC19 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DNAJC19 are known to be pathogenic (PMID: 16055927, 27928778). This variant is present in population databases (rs137854888, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with dilated cardiomyopathy with ataxia syndrome in many families (PMID: 16055927). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1951). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
PreventionGenetics, part of Exact Sciences RCV003415625 SCV004113791 pathogenic DNAJC19-related disorder 2023-06-15 criteria provided, single submitter clinical testing The DNAJC19 c.130-1G>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been reported in the homozygous state in individuals of Hutterite ancestry with autosomal recessive dilated cardiomyopathy with ataxia (Davey et al. 2006. PubMed ID: 16055927). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-180704811-C-G). Variants that disrupt the consensus splice acceptor site in DNAJC19 are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM RCV000002028 SCV000022186 pathogenic 3-methylglutaconic aciduria type 5 2012-10-05 no assertion criteria provided literature only

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