ClinVar Miner

Submissions for variant NM_000751.3(CHRND):c.1345_1346del (p.Met449fs) (rs1553575435)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627608 SCV000748608 likely pathogenic not provided 2018-04-25 criteria provided, single submitter clinical testing The c.1345_1346delAT variant in the CHRND gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1345_1346delAT variant causes a frameshift starting with codon Methionine 449, changes this amino acid to a Glutamic Acid residue, and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Met449GlufsX8. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1345_1346delAT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1345_1346delAT as a likely pathogenic variant.
Invitae RCV000812890 SCV000953220 uncertain significance Lethal multiple pterygium syndrome 2018-11-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CHRND gene (p.Met449Glufs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 69 amino acids of the CHRND protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHRND-related conditions. ClinVar contains an entry for this variant (Variation ID: 524112). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the CHRND protein. Other variant(s) that disrupt this region (p.Arg464*) have been observed in individuals with CHRND-related conditions (PMID:18252226). This suggests that this may be a clinically significant region of the protein. 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.

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