Submissions for variant NM_000214.3(JAG1):c.814G>A (p.Val272Ile)

gnomAD frequency: 0.00041  dbSNP: rs148990028

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000244534	SCV000320226	uncertain significance	Cardiovascular phenotype	2015-11-05	criteria provided, single submitter	clinical testing	The p.V272I variant (also known as c.814G>A), located in coding exon 6 of the JAG1 gene, results from a G to A substitution at nucleotide position 814. The valine at codon 272 is replaced by isoleucine, an amino acid with highly similar properties. Another alteration affecting the same amino acid, p.V272F (c.814G>T), has been previously reported in association with tetralogy of Fallot (Kola S et al. Clin Chim Acta. 2011;412(23-24):2232-6). The p.V272I variant was previously reported in the SNPDatabase as rs148990028. Based on data from ExAC, the A allele has an overall frequency of approximately 0.01% (23/121252). The highest observed frequency was approximately 0.1% (11/10390) of African alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed October 12, 2015]). Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.03% (4/13006) total alleles studied, having been observed in 0.09% (4/4406) African American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081833	SCV000645536	likely benign	Alagille syndrome due to a JAG1 point mutation	2023-11-10	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000597837	SCV000703842	uncertain significance	not provided	2018-06-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000597837	SCV001825168	likely benign	not provided	2018-10-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004547640	SCV004737481	likely benign	JAG1-related disorder	2022-04-12	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).