Submissions for variant NM_007272.3(CTRC):c.46A>G (p.Ser16Gly)

gnomAD frequency: 0.00001  dbSNP: rs765777463

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000363743	SCV000349075	likely benign	Hereditary pancreatitis	2018-01-12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000363743	SCV001561664	uncertain significance	Hereditary pancreatitis	2020-10-15	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs765777463, ExAC 0.005%). This sequence change replaces serine with glycine at codon 16 of the CTRC protein (p.Ser16Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. 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. 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 CTRC protein function. This variant has not been reported in the literature in individuals with CTRC-related conditions. ClinVar contains an entry for this variant (Variation ID: 292905).
Ambry Genetics	RCV000363743	SCV004000172	uncertain significance	Hereditary pancreatitis	2023-03-23	criteria provided, single submitter	clinical testing	The p.S16G variant (also known as c.46A>G), located in coding exon 2 of the CTRC gene, results from an A to G substitution at nucleotide position 46. The serine at codon 16 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.