Submissions for variant NM_000784.4(CYP27A1):c.83A>C (p.Lys28Thr)

gnomAD frequency: 0.00006  dbSNP: rs371449777

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000591741	SCV000706932	uncertain significance	not provided	2017-03-13	criteria provided, single submitter	clinical testing
Invitae	RCV001054067	SCV001218360	uncertain significance	Cholestanol storage disease	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 28 of the CYP27A1 protein (p.Lys28Thr). This variant is present in population databases (rs371449777, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CYP27A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 500828). 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 CYP27A1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV000591741	SCV001790461	uncertain significance	not provided	2019-06-26	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Ambry Genetics	RCV003160044	SCV003871170	uncertain significance	Inborn genetic diseases	2023-03-02	criteria provided, single submitter	clinical testing	The c.83A>C (p.K28T) alteration is located in exon 1 (coding exon 1) of the CYP27A1 gene. This alteration results from a A to C substitution at nucleotide position 83, causing the lysine (K) at amino acid position 28 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252221	SCV001427972	likely benign	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001054067	SCV002076360	uncertain significance	Cholestanol storage disease	2019-11-11	no assertion criteria provided	clinical testing