ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.10348-6C>G (rs193922837)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000119410 SCV000343561 pathogenic not provided 2017-08-15 criteria provided, single submitter clinical testing
Invitae RCV000535801 SCV000659748 pathogenic RYR1-Related Disorders 2018-07-09 criteria provided, single submitter clinical testing This sequence change falls in intron 68 of the RYR1 gene. It does not directly change the encoded amino acid sequence of the RYR1 protein. This variant is present in population databases (rs193922837, ExAC 0.02%). This variant has been reported in the compound heterozygous state with loss of function variants in multiple individuals affected with congenital myopathy (PMID: 18253926, 20839240, 21062345). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has also been reported to co-occur in cis with a missense change (p.Val4842Met). ClinVar contains an entry for this variant (Variation ID: 132994). Experimental studies have shown that this intronic change causes aberrant splicing of the RYR1 transcript and leads to a frameshift (PMID: 18253926). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000624604 SCV000741380 likely pathogenic Inborn genetic diseases 2016-03-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
PreventionGenetics,PreventionGenetics RCV000119410 SCV000852208 pathogenic not provided 2015-09-15 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763427 SCV000894192 pathogenic Myopathy, Central Core; Malignant hyperthermia, susceptibility to, 1; Minicore myopathy; Congenital myopathy with fiber type disproportion 2018-10-31 criteria provided, single submitter clinical testing
Leiden Muscular Dystrophy (RYR1) RCV000119410 SCV000154317 not provided not provided no assertion provided not provided

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