ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.3756+9G>T (rs191746041)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150588 SCV000197875 uncertain significance not specified 2014-08-05 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign.
Genetic Services Laboratory, University of Chicago RCV000150588 SCV000247243 uncertain significance not specified 2015-05-26 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000150588 SCV000334118 likely benign not specified 2015-08-27 criteria provided, single submitter clinical testing
Invitae RCV000528464 SCV000649668 benign Dysferlinopathy 2018-01-03 criteria provided, single submitter clinical testing
GeneDx RCV000150588 SCV000730590 likely benign not specified 2017-09-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000528464 SCV000914941 uncertain significance Dysferlinopathy 2018-11-15 criteria provided, single submitter clinical testing The DYSF c.3702+9G>T variant has been reported in one study and in one patient in a compound heterozygous state with a missense variant (Nilsson et al. 2013). Control data are not available for this variant, which is reported at a frequency of 0.01327 in the Mandinka in Gambia population of the 1000 Genomes Project. Functional studies using immunohistochemical staining of quadriceps muscle from the patient showed an absence of membrane-bound dysferlin secondary to the intracellular aggregation of the variant protein. Quantitative RT-PCR and Western blotting showed that intracellular total mRNA and protein levels were increased two- to three-fold respectively compared to healthy controls. Human splicing finder predicts the variant to be deleterious and to destroy a donor splice site in intron 33 likely causing an excision of the coding region required for domain C2D of the protein (exon 33) (Nilsson et al. 2013). Based on the evidence, the c.3702+9G>T variant is classified as a variant of unknown significance but suspicioud for pathogenicity for dysferlinopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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