ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.4911G>T (p.Lys1637Asn) (rs141704244)

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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 RCV000080297 SCV000333448 uncertain significance not provided 2015-08-04 criteria provided, single submitter clinical testing
Invitae RCV000548178 SCV000649707 uncertain significance Dysferlinopathy 2018-01-31 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 1598 of the DYSF protein (p.Lys1598Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. It also falls at the last nucleotide of exon 43 of the DYSF coding sequence. This variant is present in population databases (rs141704244, ExAC 0.006%). This variant has been reported in the heterozygous state in an individual affected with amyloid myopathy. This individual also carried a second variant in the DYSF gene. It is unclear from this report if the two DYSF variants are in cis or in trans (PMID: 27195159). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 94331). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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