Submissions for variant NM_004817.4(TJP2):c.1258C>T (p.Arg420Cys)

gnomAD frequency: 0.00034  dbSNP: rs199761505

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155291	SCV000204977	uncertain significance	not specified	2014-05-01	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Arg397Cys varia nt in TJP2 has not been previously reported in individuals with hearing loss, bu t has been identified in 0.04% (3/8600) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs19976 1505). Arg397 is not conserved in mammals and across evolutionary distant specie s, supporting that a change at this position may be tolerated. Additional comput ational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant cannot be determined with certainty; however based upon the conservation data, we would le an towards a more likely benign role.
Fulgent Genetics, Fulgent Genetics	RCV000766064	SCV000897526	uncertain significance	Hypercholanemia, familial 1; Cholestasis, progressive familial intrahepatic, 4	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001731401	SCV001982488	uncertain significance	not provided	2023-11-13	criteria provided, single submitter	clinical testing	Identified in a patient with gallstone disease in published literature, reported as p.(R178C) using alternate nomenclature, however, additional information about genotype and phenotype was not available (PMID: 37208429); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 37208429)
Revvity Omics, Revvity	RCV001731401	SCV004238054	uncertain significance	not provided	2023-04-18	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001731401	SCV005195431	uncertain significance	not provided		criteria provided, single submitter	not provided
CeGaT Center for Human Genetics Tuebingen	RCV001731401	SCV005893766	likely benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	TJP2: BP4
PreventionGenetics, part of Exact Sciences	RCV003927508	SCV004742715	likely benign	TJP2-related disorder	2024-02-08	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).