Submissions for variant NM_001370466.1(NOD2):c.193G>A (p.Val65Ile)

gnomAD frequency: 0.00048  dbSNP: rs187264529

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001782789	SCV000397174	uncertain significance	Inflammatory bowel disease 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000268742	SCV000397175	benign	Blau syndrome	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812837	SCV001477863	uncertain significance	not provided	2020-02-16	criteria provided, single submitter	clinical testing	The NOD2 c.274G>A; p.Val92Ile variant (rs187264529), to our knowledge, is not reported in the medical literature or gene specific databases. The variant is listed in the ClinVar database (Variation ID: 319425) and in the general population with an overall allele frequency of 0.015% (43/282,598 alleles) in the Genome Aggregation Database. The valine at codon 92 is moderately conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Val92Ile variant is uncertain at this time.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002261053	SCV002542709	likely benign	Autoinflammatory syndrome	2019-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV002521017	SCV003261625	likely benign	Blau syndrome; Regional enteritis	2023-12-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002521016	SCV003530221	uncertain significance	Inborn genetic diseases	2021-07-06	criteria provided, single submitter	clinical testing	The c.274G>A (p.V92I) alteration is located in exon 2 (coding exon 2) of the NOD2 gene. This alteration results from a G to A substitution at nucleotide position 274, causing the valine (V) at amino acid position 92 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.