ClinVar Miner

Submissions for variant NM_000044.6(AR):c.2070C>G (p.His690Gln)

dbSNP: rs754583155
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001217034 SCV001388861 uncertain significance Androgen resistance syndrome; Kennedy disease 2019-05-18 criteria provided, single submitter clinical testing 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. This variant disrupts the p.His690 amino acid residue in AR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12213902; this residue is also referred to as p.His689). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with glutamine at codon 690 of the AR protein (p.His690Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine.
GeneDx RCV003317455 SCV004021590 likely pathogenic not provided 2019-05-22 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

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