Submissions for variant NM_004415.4(DSP):c.3981C>T (p.Ile1327=)

gnomAD frequency: 0.00009  dbSNP: rs397516934

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038033	SCV000061699	likely benign	not specified	2012-04-19	criteria provided, single submitter	clinical testing	The Ile1327Ile variant in exon 23 of DSP: This variant is not expected to have c linical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. The Ile1327Ile variant in exon 23 of DSP (allele frequency = n/a)
GeneDx	RCV000756043	SCV000512881	likely benign	not provided	2021-02-26	criteria provided, single submitter	clinical testing
Invitae	RCV001080154	SCV000641309	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-29	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756043	SCV000883751	likely benign	not provided	2017-05-31	criteria provided, single submitter	clinical testing	The c.3981C>T; p.Ile1327Ile variant (rs397516934, ClinVar variant ID 44898) does not alter the amino acid sequence of the DSP protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with cardiomyopathy in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.009% (identified on 24 out of 276,534 chromosomes). Based on the available information, the c.3981C>T variant is likely to be benign.
Color Diagnostics, LLC DBA Color Health	RCV001183480	SCV001349222	likely benign	Cardiomyopathy	2018-12-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354194	SCV002620804	likely benign	Cardiovascular phenotype	2019-06-06	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001183480	SCV004240527	likely benign	Cardiomyopathy	2023-02-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003894864	SCV004714798	likely benign	DSP-related condition	2023-06-20	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).