Submissions for variant NM_014762.4(DHCR24):c.731C>T (p.Pro244Leu)

gnomAD frequency: 0.00061  dbSNP: rs138667252

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725500	SCV000337362	uncertain significance	not provided	2017-04-27	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000267512	SCV000594357	uncertain significance	not specified	2017-01-09	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763975	SCV000894926	uncertain significance	Desmosterolosis	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000763975	SCV001259194	uncertain significance	Desmosterolosis	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV000725500	SCV002160668	uncertain significance	not provided	2022-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 244 of the DHCR24 protein (p.Pro244Leu). This variant is present in population databases (rs138667252, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with DHCR24-related conditions. ClinVar contains an entry for this variant (Variation ID: 284658). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DHCR24 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.
Ambry Genetics	RCV002519158	SCV003698300	uncertain significance	Inborn genetic diseases	2022-01-31	criteria provided, single submitter	clinical testing	The c.731C>T (p.P244L) alteration is located in exon 5 (coding exon 5) of the DHCR24 gene. This alteration results from a C to T substitution at nucleotide position 731, causing the proline (P) at amino acid position 244 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.