Submissions for variant NM_002230.4(JUP):c.1815C>T (p.Ala605=)

gnomAD frequency: 0.00001  dbSNP: rs543862977

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590680	SCV000699464	benign	not provided	2016-04-26	criteria provided, single submitter	clinical testing	Variant summary: The JUP c.1815C>T variant affects a non-conserved nucleotide, resulting in no amino acid change. Mutation Taster predicts a damaging outcome for this variant, but 5/5 Alamut algorithms predict no significant change to splicing. This variant was found in 4/115552 control chromosomes at a frequency of 0.0000346, which is about 3 times the maximal expected frequency of a pathogenic JUP allele (0.00001); the variant was found in mainly in South Asians (3/15146 S. Asian chromosomes; MAF 0.0002, which is 20-fold greater than the maximal expected pathogenic JUP allele frequency), suggesting this variant is benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as benign.
Illumina Laboratory Services, Illumina	RCV001124646	SCV001283629	uncertain significance	Naxos disease	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	RCV001124647	SCV001283630	uncertain significance	Arrhythmogenic right ventricular dysplasia 12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001463938	SCV001667894	likely benign	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2024-01-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000590680	SCV001786453	likely benign	not provided	2020-09-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002413667	SCV002711021	likely benign	Cardiovascular phenotype	2019-01-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.