ClinVar Miner

Submissions for variant NM_004393.6(DAG1):c.1708G>A (p.Val570Met)

gnomAD frequency: 0.00006  dbSNP: rs370669533
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498181 SCV000589424 uncertain significance not provided 2018-06-27 criteria provided, single submitter clinical testing The V570M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 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 V570M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001043597 SCV001207352 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2P; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 570 of the DAG1 protein (p.Val570Met). This variant is present in population databases (rs370669533, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 431866). 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 not expected to disrupt DAG1 protein function. 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.
Revvity Omics, Revvity Omics RCV000498181 SCV003834228 uncertain significance not provided 2021-11-11 criteria provided, single submitter clinical testing

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