ClinVar Miner

Submissions for variant NM_004393.6(DAG1):c.220G>A (p.Val74Ile)

gnomAD frequency: 0.00004  dbSNP: rs189360006
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001857671 SCV002270367 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2P; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 2022-09-03 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 74 of the DAG1 protein (p.Val74Ile). This variant is present in population databases (rs189360006, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of muscular dystrophy-dystroglycanopathy (PMID: 25503980). ClinVar contains an entry for this variant (Variation ID: 208540). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects DAG1 function (PMID: 25503980). 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 RCV003144154 SCV003830417 uncertain significance not provided 2021-09-15 criteria provided, single submitter clinical testing
OMIM RCV000190545 SCV000245426 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2P 2015-01-20 no assertion criteria provided literature only

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