Submissions for variant NM_000784.4(CYP27A1):c.789C>T (p.Pro263=)

gnomAD frequency: 0.00019  dbSNP: rs143600636

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000358090	SCV000427470	uncertain significance	Cholestanol storage disease	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000358090	SCV000744172	likely benign	Cholestanol storage disease	2017-06-28	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000728807	SCV000856423	uncertain significance	not provided	2018-02-06	criteria provided, single submitter	clinical testing
Invitae	RCV000358090	SCV001043040	likely benign	Cholestanol storage disease	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000728807	SCV001783764	likely benign	not provided	2020-11-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002418198	SCV002676600	likely benign	Cardiovascular phenotype	2020-03-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
CeGaT Center for Human Genetics Tuebingen	RCV000728807	SCV004151405	likely benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	CYP27A1: BP4, BP7
Natera, Inc.	RCV000358090	SCV001462721	likely benign	Cholestanol storage disease	2020-04-25	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001700067	SCV001917928	benign	not specified		no assertion criteria provided	clinical testing