Submissions for variant NM_001159773.2(CANT1):c.1172G>A (p.Gly391Glu)

gnomAD frequency: 0.00268  dbSNP: rs34082669

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000426567	SCV000516747	uncertain significance	not provided	2017-01-19	criteria provided, single submitter	clinical testing	The G391E variant in the CANT gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not reported in the homozygous state, the NHLBI ESP Exome Sequencing Project reports G391E was observed in 0.37% (32/8600 alleles) from individuals of European American background, indicating it may be a rare variant in this population. The G391E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G391E as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000426567	SCV001023102	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001124606	SCV001283579	likely benign	Desbuquois dysplasia 1	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	RCV000426567	SCV001470846	uncertain significance	not provided	2019-11-03	criteria provided, single submitter	clinical testing	The CANT1 c.1172G>A; p.Gly391Glu variant (rs34082669), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 379568). This variant is found in the genera population with an overall allele frequency of 0.23% (663/282882 alleles, including a single homozygote) in the Genome Aggregation Database. The glycine at codon 391 is highly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Gly391Glu variant is uncertain at this time.
PreventionGenetics, part of Exact Sciences	RCV003922730	SCV004743611	likely benign	CANT1-related disorder	2023-01-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).