ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.4911G>A (p.Lys1637=)

dbSNP: rs141704244
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000387010 SCV000342093 uncertain significance not provided 2016-05-12 criteria provided, single submitter clinical testing
Invitae RCV001241552 SCV001414578 uncertain significance Qualitative or quantitative defects of dysferlin 2022-04-27 criteria provided, single submitter clinical testing This sequence change affects codon 1598 of the DYSF mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DYSF protein. This variant also falls at the last nucleotide of exon 43, which is part of the consensus splice site for this exon. This variant is present in population databases (rs141704244, gnomAD 0.05%). This variant has been observed in individual(s) with limb-girdle muscular dystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 288089). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.4794G nucleotide in the DYSF gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 27195159). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV001828247 SCV004047096 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B criteria provided, single submitter clinical testing The synonymous variant p.K1637= in DYSF (NM_001130987.2) has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. It has not been reported in affected individuals. This p.Lys1637 type of mutation causes no change in the protein that is produced, which is why it's considered as synonymous mutation. This variant also falls at the last nucleotide of exon 43 of the DYSF coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (Buratti et al, 2007, Zhang et al, 1998). The nucleotide c.4911 in DYSF is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. In the absence of another reportable variant molecular diagnosis is not confirmed.
Natera, Inc. RCV001828247 SCV002082348 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2019-10-28 no assertion criteria provided clinical testing

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