Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000666231 | SCV000790489 | uncertain significance | Congenital lipoid adrenal hyperplasia due to STAR deficency | 2017-04-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001855455 | SCV002234809 | pathogenic | not provided | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 192 of the STAR protein (p.Arg192Cys). This variant is present in population databases (rs752311616, gnomAD 0.003%). This missense change has been observed in individual(s) with nonclassic lipoid adrenal hyperplasia (PMID: 19773404). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 551230). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STAR protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects STAR function (PMID: 20444910). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000666231 | SCV004038287 | pathogenic | Congenital lipoid adrenal hyperplasia due to STAR deficency | 2023-08-07 | criteria provided, single submitter | clinical testing | Variant summary: STAR c.574C>T (p.Arg192Cys) results in a non-conservative amino acid change located in the START domain (IPR002913) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251364 control chromosomes. c.574C>T has been reported in the literature in multiple individuals affected with Congenital Lipoid Adrenal Hyperplasia (Metherell_2009). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence demonstrating a decrease in activity and Cholesterol binding (Sahakitrungruang_2010). The following publications have been ascertained in the context of this evaluation (PMID: 19773404, 20444910). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic. |