Submissions for variant NM_004415.4(DSP):c.1344G>A (p.Leu448=)

gnomAD frequency: 0.00019  dbSNP: rs138226280

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181255	SCV000233535	benign	not specified	2014-08-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000227634	SCV000288525	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621322	SCV000736836	likely benign	Cardiovascular phenotype	2017-02-21	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.
Color Diagnostics, LLC DBA Color Health	RCV000771824	SCV000904530	likely benign	Cardiomyopathy	2018-04-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001162536	SCV001324492	uncertain significance	Woolly hair-skin fragility syndrome	2019-02-07	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001164569	SCV001326702	uncertain significance	Lethal acantholytic epidermolysis bullosa	2019-02-07	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001164570	SCV001326703	uncertain significance	Arrhythmogenic right ventricular dysplasia 8	2019-02-07	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000181255	SCV001365491	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Leu448Leu in Exon 11 of DSP: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the splice consensus sequence. It has been identified in 0.1% (6/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs138226280).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000181255	SCV002051251	benign	not specified	2021-12-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001701700	SCV004163039	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	DSP: BP4
PreventionGenetics, part of Exact Sciences	RCV003937647	SCV004756592	likely benign	DSP-related condition	2019-06-05	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).
Clinical Genetics, Academic Medical Center	RCV000181255	SCV001924021	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701700	SCV001931227	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001701700	SCV001955110	likely benign	not provided		no assertion criteria provided	clinical testing