Submissions for variant NM_004415.4(DSP):c.5593A>T (p.Asn1865Tyr)

gnomAD frequency: 0.00001  dbSNP: rs562015789

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000272334	SCV000465138	likely benign	Arrhythmogenic right ventricular dysplasia 8	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000308765	SCV000465139	likely benign	Lethal acantholytic epidermolysis bullosa	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000268654	SCV000465141	likely benign	Woolly hair-skin fragility syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV001084945	SCV000555770	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000481903	SCV000568983	likely benign	not provided	2020-09-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21636032)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000481903	SCV000885323	uncertain significance	not provided	2018-06-20	criteria provided, single submitter	clinical testing	The p.Asn1865Tyr variant (rs562015789) was reported in one individual from a healthy cohort of 427 subjects of various ethnic backgrounds (Kapplinger 211). This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.3 percent in the South Asian population (identified on 99 out of 30,782 chromosomes, including 1 homozygote), and has been reported to the ClinVar database (Variation ID: 357959). The asparagine at position 1865 is moderately conserved considering 12 species (Alamut v2.11) and computational analyses of the p.Asn1865Tyr variant on protein structure and function indicates a deleterious effect (SIFT: damaging, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Asn1865Tyr variant with certainty.
Color Diagnostics, LLC DBA Color Health	RCV000771806	SCV000904507	likely benign	Cardiomyopathy	2018-10-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002348111	SCV002649154	likely benign	Cardiovascular phenotype	2019-06-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
PreventionGenetics, part of Exact Sciences	RCV003902393	SCV004727086	likely benign	DSP-related condition	2022-02-27	criteria provided, single submitter	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).