ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.6116G>A (p.Arg2039Gln) (rs115407852)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487973 SCV000575218 likely pathogenic not provided 2016-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000675073 SCV000800565 uncertain significance Limb-girdle muscular dystrophy, type 2B 2017-07-27 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000356385 SCV000341726 likely benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Invitae RCV000525944 SCV000649734 uncertain significance Dysferlinopathy 2016-05-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2000 of the DYSF protein (p.Arg2000Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs115407852, ExAC 0.04%). This variant was reported in an individual affected with Miyoshi myopathy (PMID: 11468312, 22194990) and in a family affected with limb girdle muscular dystrophy, type 2 (PMID: 20623375).  In this family, both the proband and an unaffected relative were found to be homozygous for this variant,  Additionally, a variant in an additional gene was found to segregate with disease in this family, leading the authors to suggest that the p.Arg2000Gln variant was not disease causing in this family (PMID: 20623375). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both unaffected and affected individuals, and the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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