ClinVar Miner

Submissions for variant NM_000044.6(AR):c.2678C>A (p.Pro893Gln)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000802143 SCV000941961 uncertain significance Androgen resistance syndrome; Bulbo-spinal atrophy X-linked 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces proline with glutamine at codon 893 of the AR protein (p.Pro893Gln). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with AR-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Pro893 amino acid residue in AR. Other variant(s) that disrupt this residue have been observed in affected individuals, suggesting that it is a clinically significant residue (PMID: 25674389, 29785970, 15925895). As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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