ClinVar Miner

Submissions for variant NM_000781.3(CYP11A1):c.940G>A (p.Glu314Lys) (rs6161)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413593 SCV000490512 likely pathogenic not provided 2016-05-10 criteria provided, single submitter clinical testing The E314K variant has been reported previously in two unrelated individuals with primary adrenal insufficiency; one individual harbored another CYP11A1 variant in trans whereas the other reported individual had no other molecular findings (Chan et al., 2015). Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports E314K was observed in 0.34% (29/8,592) alleles from individuals of European American ancestry. The E314K 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, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The E314K variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000413593 SCV001036285 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Mendelics RCV000989359 SCV001139655 uncertain significance Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000989359 SCV001277696 likely benign Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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