ClinVar Miner

Submissions for variant NM_004408.4(DNM1):c.889C>T (p.Arg297Trp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003091675 SCV003477562 uncertain significance Developmental and epileptic encephalopathy, 31A 2022-10-25 criteria provided, single submitter clinical testing 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. 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 DNM1 protein function. This missense change has been observed in individual(s) with clinical features of DNM1-related conditions (PMID: 33004838). 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 sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 297 of the DNM1 protein (p.Arg297Trp).
PreventionGenetics, part of Exact Sciences RCV003410078 SCV004114026 uncertain significance DNM1-related disorder 2023-05-15 criteria provided, single submitter clinical testing The DNM1 c.889C>T variant is predicted to result in the amino acid substitution p.Arg297Trp. This variant has been reported in an individual with a neurodevelopmental presentation, but no additional clinical details were provided (Supp. Data 5, Wang et al 2020. PubMed ID: 33004838). This variant is reported in 2 of ~283,000 alleles in gnomAD: However, the gnomAD NGS read data displays skewing in individuals heterozygous for this variant and should be interpreted with caution (http://gnomad.broadinstitute.org/variant/9-130984515-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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