ClinVar Miner

Submissions for variant NM_001134831.2(AHI1):c.2156A>G (p.Asp719Gly) (rs863225134)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000201556 SCV000256254 pathogenic Joubert syndrome 3 2015-02-23 criteria provided, single submitter research
GeneDx RCV000497534 SCV000589649 likely pathogenic not provided 2016-02-10 criteria provided, single submitter clinical testing The D719G variant has been reported previously as a homozygous variant in two siblings with Joubert syndrome and was classified as presumed causal for these individuals (Bachmann-Gagescu et al., 2015; Parisi et al., 2006). Missense variants in nearby residues (R723Q and W725R) have also been reported in the Human Gene Mutation Database in association with Joubert syndrome (Stenson et al., 2014). The D719G variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This 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. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the D719G variant is damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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