ClinVar Miner

Submissions for variant NM_004393.6(DAG1):c.1186A>G (p.Thr396Ala)

gnomAD frequency: 0.00002  dbSNP: rs779846682
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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 RCV000648790 SCV000770611 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2P; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 2017-08-10 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 396 of the DAG1 protein (p.Thr396Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs779846682, ExAC 0.001%). This variant has not been reported in the literature in individuals with DAG1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV002269297 SCV002552969 uncertain significance not provided 2022-01-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21388311)
Ambry Genetics RCV002533359 SCV003703463 uncertain significance Inborn genetic diseases 2021-09-16 criteria provided, single submitter clinical testing The c.1186A>G (p.T396A) alteration is located in exon 3 (coding exon 2) of the DAG1 gene. This alteration results from a A to G substitution at nucleotide position 1186, causing the threonine (T) at amino acid position 396 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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