Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001055649 | SCV001220049 | likely pathogenic | Duchenne muscular dystrophy | 2022-08-02 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Cys3337 amino acid residue in DMD. Other variant(s) that disrupt this residue have been observed in individuals with DMD-related conditions (PMID: 17726484, 19959795, 26911353), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 851285). This missense change has been observed in individuals with DMD-related muscular dystrophy (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 3337 of the DMD protein (p.Cys3337Phe). |
ARUP Laboratories, |
RCV001811633 | SCV001473858 | uncertain significance | not provided | 2020-01-23 | criteria provided, single submitter | clinical testing | The DMD c.10010G>T, p.Cys3337Phe variant, to our knowledge, is not reported in the medical literature or gene specific databases, however other changes at this codon have been reported in DMD patients (Torella 2010). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The cysteine at codon 3337 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Cys3337Phe variant is uncertain at this time. References: Monaco et al. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics. 1988; 2(1): 90-95. Torella et al. One hundred twenty-one dystrophin point mutations detected from stored DNA samples by combinatorial denaturing high-performance liquid chromatography. J Mol Diagn. 2010 Jan;12(1):65-73. Gene statement: Pathogenic variants in DMD are inherited in an X-linked manner and are associated with Duchenne muscular dystrophy (MIM: 310200), Becker muscular dystrophy (MIM: 300376), and dilated cardiomyopathy (MIM: 302045). |
Natera, |
RCV001832504 | SCV002077633 | uncertain significance | Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency | 2019-06-27 | no assertion criteria provided | clinical testing |