ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1012C>T (p.Arg338Ter)

gnomAD frequency: 0.00001  dbSNP: rs759761559
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics Laboratory, Skane University Hospital Lund RCV000488375 SCV005197517 likely pathogenic not provided 2022-07-13 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV001030775 SCV002580988 pathogenic Congenital myotonia, autosomal recessive form 2022-06-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000701179 SCV000829965 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-11-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg338*) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive myotonia congenita (PMID: 22521272, 24452722, 27118449). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 425428). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000488375 SCV000575537 likely pathogenic not provided 2016-11-01 criteria provided, single submitter clinical testing
Section for Clinical Neurogenetics, University of Tübingen RCV001030775 SCV001156082 pathogenic Congenital myotonia, autosomal recessive form 2019-08-01 no assertion criteria provided research

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