Submissions for variant NM_203486.3(DLL3):c.677C>G (p.Pro226Arg)

gnomAD frequency: 0.00034  dbSNP: rs145191532

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000363667	SCV000340415	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001134170	SCV001293899	likely benign	Syndactyly	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001134171	SCV001293900	likely benign	Spondylocostal dysostosis 1, autosomal recessive	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001134171	SCV001471617	uncertain significance	Spondylocostal dysostosis 1, autosomal recessive	2020-08-24	criteria provided, single submitter	clinical testing	The DLL3 c.677C>G; p.Pro226Arg variant (rs145191532), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 286841). This variant is found in the South Asian population with an allele frequency of 0.40% (121/30616 alleles) in the Genome Aggregation Database. The proline at codon 226 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. While the relatively high population frequency suggests that this may be a benign variant, given the lack of clinical and functional data, the significance of the p.Pro226Arg variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001518609	SCV001727339	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001518609	SCV001793485	likely benign	not provided	2020-08-28	criteria provided, single submitter	clinical testing