ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.1718G>A (p.Arg573Gln)

gnomAD frequency: 0.00002  dbSNP: rs755829878
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001326184 SCV001517202 uncertain significance Qualitative or quantitative defects of dysferlin 2021-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 555 of the DYSF protein (p.Arg555Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DYSF-related conditions. ClinVar contains an entry for this variant (Variation ID: 684441). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYSF protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg555 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17698709, 22174839, 25591676, 27066573). This suggests that this residue is clinically significant, and that variants that disrupt this residue 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.
Ambry Genetics RCV004973025 SCV005571609 uncertain significance Inborn genetic diseases 2024-11-26 criteria provided, single submitter clinical testing The c.1664G>A (p.R555Q) alteration is located in exon 19 (coding exon 19) of the DYSF gene. This alteration results from a G to A substitution at nucleotide position 1664, causing the arginine (R) at amino acid position 555 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect, ClinGen RCV000844895 SCV000986697 not provided Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Distal myopathy with anterior tibial onset no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 10/21/2016 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Natera, Inc. RCV001825702 SCV002079825 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-08-10 no assertion criteria provided clinical testing

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