Submissions for variant NM_002230.4(JUP):c.2038_2039del (p.Trp680fs)

dbSNP: rs113994177

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481302	SCV000566100	pathogenic	not provided	2015-04-08	criteria provided, single submitter	clinical testing	The c.2038_2039delTG variant is expected to result in either an abnormal, truncated proteinproduct or loss of protein from this allele through nonsense-mediated mRNA decay. The c.2038_2039delTGvariant has been reported previously in multiple individuals with Naxos disease, an autosomal recessivedisorder identified in Naxos, Greece, and characterized by ARVC, palmoplantar keratoderma, and woolly hair(McKoy G et al., 2000; Antoniades L et al.., 2006; Lazaros G et al., 2009). These studies show that allindividuals who are homozygous for the c.2038_2039delTG (reported as 2157del2 due to alternatenomenclature) are affected with Naxos disease and all individuals who are heterozygous are unaffected(McKoy et al., 2000; Antoniades et al., 2006). In summary, c.2038_2039delTG in the JUP gene is interpreted as a pathogenic variant.
Revvity Omics, Revvity	RCV000481302	SCV002023198	pathogenic	not provided	2019-10-08	criteria provided, single submitter	clinical testing
Invitae	RCV003764573	SCV004571428	pathogenic	Naxos disease; Arrhythmogenic right ventricular dysplasia 12	2023-10-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp680Glyfs*11) in the JUP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acid(s) of the JUP protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive Naxos disease (PMID: 10902626). It has also been observed to segregate with disease in related individuals. This variant is also known as 2157del2 or c.2157delTG-G680fsX690. ClinVar contains an entry for this variant (Variation ID: 13599). This variant disrupts a region of the JUP protein in which other variant(s) (p.Pro736Leu) have been observed in individuals with JUP-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000014569	SCV000034823	pathogenic	Naxos disease	2000-06-17	no assertion criteria provided	literature only
GeneReviews	RCV001731287	SCV000040898	not provided	Arrhythmogenic right ventricular dysplasia 12		no assertion provided	literature only