Submissions for variant NM_000784.4(CYP27A1):c.1151C>T (p.Pro384Leu)

gnomAD frequency: 0.01478  dbSNP: rs41272687

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179342	SCV000231576	benign	not specified	2014-12-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000179342	SCV000305516	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000179342	SCV000518722	benign	not specified	2016-10-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000179342	SCV000538767	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP(all): 241/13006=1.8%
Athena Diagnostics	RCV000179342	SCV000613049	benign	not specified	2017-07-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000056071	SCV001136217	likely benign	Cholestanol storage disease	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000056071	SCV001298202	uncertain significance	Cholestanol storage disease	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000056071	SCV001435237	benign	Cholestanol storage disease		criteria provided, single submitter	research	The heterozygous p.Pro384Leu variant in CYP27A1 has been identified in 4 individuals with cerebrotendinous xanthomatosis in cis with a frameshift mutation upstream of the variant (PMID: 10775536), and has also been identified in >3% of South Asian chromosomes and 37 total homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for cerebrotendinous xanthomatosis.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000056071	SCV001732808	benign	Cholestanol storage disease	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000056071	SCV001736819	benign	Cholestanol storage disease	2021-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000179342	SCV002050910	likely benign	not specified	2021-12-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345362	SCV002620500	benign	Cardiovascular phenotype	2020-10-05	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneReviews	RCV000056071	SCV000087134	pathologic	Cholestanol storage disease	2013-08-01	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GenomeConnect, ClinGen	RCV000056071	SCV001338877	not provided	Cholestanol storage disease		no assertion provided	phenotyping only	Variant interpretted as Pathogenic and reported on 05-03-2012 by Lab or GTR ID 504843. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Clinical Genetics, Academic Medical Center	RCV001698579	SCV001917014	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001698579	SCV001963340	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001698579	SCV001978193	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001698579	SCV002037002	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000056071	SCV002078799	benign	Cholestanol storage disease	2019-11-01	no assertion criteria provided	clinical testing