ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.6025C>T (p.Pro2009Ser)

dbSNP: rs1057521141
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000424011 SCV000521198 likely pathogenic not provided 2016-02-29 criteria provided, single submitter clinical testing The P1970S variant in the DYSF gene has been reported previously in association with limb girdle muscular dystrophy type 2B (LGMD2B) and absence of dysferlin on muscle biopsy by immunohistochemistry or Western blot (Krahn et al., 2009; Walsh et al., 2011). The P1970S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P1970S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The P1970S variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV001861509 SCV002245904 pathogenic Qualitative or quantitative defects of dysferlin 2021-01-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with limb-girdle muscular dystrophy type 2B (PMID: 18853459, 27666772, 21484829). ClinVar contains an entry for this variant (Variation ID: 381677). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 1970 of the DYSF protein (p.Pro1970Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine.
Baylor Genetics RCV003470383 SCV004192279 pathogenic Miyoshi muscular dystrophy 1 2022-11-15 criteria provided, single submitter clinical testing
Counsyl RCV000671182 SCV000796133 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2017-12-07 no assertion criteria provided clinical testing
Natera, Inc. RCV000671182 SCV002080343 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2021-03-17 no assertion criteria provided clinical testing

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