Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000307005 | SCV000427466 | likely pathogenic | Cholestanol storage disease | 2017-04-27 | criteria provided, single submitter | clinical testing | The CYP27A1 c.525delG (p.Asp176MetfsTer6) variant, also known as c.526delG, results in a frameshift, and is predicted to result in premature termination of the protein. The p.Asp176MetfsTer6 variant has been reported in four studies in which it is found in a total of five individuals with cerebrotendinous xanthomatosis, including two siblings, all of whom were homozygous for the variant (Verrips et al. 1996; Clayton et al. 2002; Shah et al. 2012; Dutta et al. 2015). The variant has also been reported in a heterozygous state in one unaffected individual. Control data are unavailable for this variant which is reported at a frequency of 0.00012 in the South Asian population of the Exome Aggregation Consortium, but this is based on two alleles only in a region of good sequence coverage so the variant is presumed rare. Due to the potential impact of frameshift variants and the supporting evidence from the literature, the p.Asp176MetfsTer6 variant is classified as likely pathogenic for cerebrotendinous xanthomatosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV000307005 | SCV001586476 | pathogenic | Cholestanol storage disease | 2023-05-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp176Metfs*6) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 334367). This variant is also known as c.546del. This premature translational stop signal has been observed in individuals with cerebrotendinous xanthomatosis (PMID: 8931710, 26937392). This variant is present in population databases (rs765512351, gnomAD 0.03%). |
Fulgent Genetics, |
RCV000307005 | SCV002801302 | pathogenic | Cholestanol storage disease | 2022-01-05 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000307005 | SCV002820230 | pathogenic | Cholestanol storage disease | criteria provided, single submitter | clinical testing | This variant causes a frameshift starting with codon Aspartic Acid 176, changes this amino acid to Methionine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Asp176MetfsTer6. This variant has been previously reported in affected patients and has segregated with disease (Dutta AK et al, Shah K et al, Clayton PT et al). The variant has been reported to ClinVar as Pathogenic. The p.Asp176MetfsTer6 variant is novel (not in any individuals) in 1000 Genomes and is present at a frequency of 0.00012 in South Asian population in the gnomad database. The variant is predicted to cause loss of function due to protein truncation. Loss of function variants have been previously reported to be disease causing. Hence the above variant has been classified as Pathogenic. | |
Revvity Omics, |
RCV000307005 | SCV003819406 | pathogenic | Cholestanol storage disease | 2022-03-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003422309 | SCV004117517 | pathogenic | CYP27A1-related condition | 2022-09-22 | criteria provided, single submitter | clinical testing | The CYP27A1 c.526delG variant is predicted to result in a frameshift and premature protein termination (p.Asp176Metfs*6). This variant was reported in the homozygous state in individuals with cerebrotendinous xanthomatosis (reported as G deletion at position 546 or 547 in Verrips et al. 1996. PubMed ID: 8931710; Dutta et al. 2015. PubMed ID: 26937392). This variant is reported in 0.026% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-219677022-CG-C). Frameshift variants in CYP27A1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Baylor Genetics | RCV000307005 | SCV004192641 | pathogenic | Cholestanol storage disease | 2023-10-24 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000307005 | SCV000087197 | pathologic | Cholestanol storage disease | 2013-08-01 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Counsyl | RCV000307005 | SCV001132161 | pathogenic | Cholestanol storage disease | 2017-10-17 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000307005 | SCV002078772 | pathogenic | Cholestanol storage disease | 2021-01-19 | no assertion criteria provided | clinical testing |