ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.3498T>A (p.Tyr1166Ter) (rs758944159)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000385716 SCV000335160 pathogenic not provided 2016-12-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000407800 SCV000431793 likely pathogenic Dysferlinopathy 2017-04-27 criteria provided, single submitter clinical testing The DYSF c.3444T>A (p.Tyr1148Ter) stop-gained variant has not been reported in the literature; however variants that are predicted to have the same functional consequence as the c.3444T>A (p.Tyr1148Ter) variant have been associated with DYSF-related disorders including limb-girdle muscular dystrophy (LGMD) and Miyoshi myopathy (MM). Three studies have been published in which the p.Tyr1148Ter variant is found in a total of five individuals including two in a homozygous state and three in a compound heterozygous state (Kawabe et al. 2004; Klinge et al. 2010; Dominov et al. 2014). Kawabe et al. (2004) identified two related individuals, one with LGMD and one with MM who were homozygous for a DYSF c.3817-8TG>AA (p. Tyr1148Ter) variant. Klinge et al. (2010) identified an individual with MM who was compound heterozygous for a DYSF c.3444_3445delinsAA (p.Tyr1148Ter) variant and a second missense variant. Dominov et al. (2014) observed a DYSF c.3444_3445delTGinsAA (p.Tyr1148Ter) variant in two siblings with MM who were compound heterozygous for the variant and a second insertion variant. The c.3817-8TG>AA (p. Tyr1148Ter) variant was absent from 120 ethnically matched controls (Kawabe et al. 2004). Control data are unavailable for the c.3444T>A (p.Tyr1148Ter) variant and the c.3444_3445delinsAA (p.Tyr1148Ter) variant. The c.3444T>A (p.Tyr1148Ter) variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Due to the potential impact of stop-gained variants and the evidence, the c.3444T>A (p.Tyr1148Ter) variant is classified as likely pathogenic for dysferlinopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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