ClinVar Miner

Submissions for variant NM_153033.4(KCTD7):c.280C>T (p.Arg94Trp) (rs387907260)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Undiagnosed Diseases Network,NIH RCV000030687 SCV000746646 likely pathogenic Epilepsy, progressive myoclonic 3 2017-08-22 criteria provided, single submitter clinical testing Heterozygous c.280C>T (p.R94W) likely pathogenic variant and c.456G>A (p.V152V) variant of unknown clinical significance in the KCTD7 gene were detected by exome sequencing and confirmed by Sanger sequencing this individual and her similarly affected younger brother. The c.280C>T (p.R94W) likely pathogenic variant has been previously reported in the homozygous state in two apparently unrelated Turkish patients [PMID 22693283, 22606975]. The potential pathogenicity of the variant is also supported by a recent functional study [PMID 27742667]. The c.456G>A (p.V152V) variant was predicted to affect splicing by in silico modeling. This effect on splicing was confirmed by RNA sequencing which showed evidence of a novel splice donor site that prematurely terminates exon 3 of KCTD7 in patient samples. Splicing effect was also confirmed by Sanger sequencing of amplified cDNA corresponding to KCTD7 exons 2-4 which showed two discrete bands in patients compared to one band in unrelated controls [Zastrow et al., ASHG 2017]. Whole exome sequencing analysis and Sanger analysis showed that the father is heterozygous for c.280C>T (p.R94W) and the mother is heterozygous for c.456G>A (p.V152V), indicating the two variants are in trans in this individual and her brother.
OMIM RCV000030687 SCV000053348 pathogenic Epilepsy, progressive myoclonic 3 2012-06-01 no assertion criteria provided literature only

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