ClinVar Miner

Submissions for variant NM_004393.6(DAG1):c.1306A>G (p.Thr436Ala)

gnomAD frequency: 0.00009  dbSNP: rs149838438
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000658321 SCV000337512 uncertain significance not provided 2018-08-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000534438 SCV000650602 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2P; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 436 of the DAG1 protein (p.Thr436Ala). This variant is present in population databases (rs149838438, 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: 284765). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV000658321 SCV000780093 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DAG1 gene. The T436A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T436A variant is observed in 15/126670 (0.01%) alleles from individuals of European background (Lek et al., 2016). The T436A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter 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.
Ambry Genetics RCV003165738 SCV003876688 uncertain significance Inborn genetic diseases 2023-01-24 criteria provided, single submitter clinical testing The c.1306A>G (p.T436A) 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 1306, causing the threonine (T) at amino acid position 436 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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