Submissions for variant NM_004415.4(DSP):c.1743C>T (p.Ala581=)

gnomAD frequency: 0.00003  dbSNP: rs139095230

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154709	SCV000204389	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Ala581Ala in exon 14 of DSP: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 1/7020 European Ame rican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs139095230). Ala581Ala in exon 14 of DSP (rs139095230; allele frequency = 1/7020) **
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231994	SCV000288529	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000335979	SCV000464902	uncertain significance	Arrhythmogenic right ventricular dysplasia 8	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000406249	SCV000464903	uncertain significance	Woolly hair-skin fragility syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000336664	SCV000464905	uncertain significance	Lethal acantholytic epidermolysis bullosa	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001171089	SCV001333760	benign	Cardiomyopathy	2018-10-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001171089	SCV001354075	likely benign	Cardiomyopathy	2018-12-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001618309	SCV001845637	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399543	SCV002712130	likely benign	Cardiovascular phenotype	2020-10-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
CeGaT Center for Human Genetics Tuebingen	RCV001618309	SCV004163043	likely benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing	DSP: BP4, BP7
All of Us Research Program, National Institutes of Health	RCV003998265	SCV004822741	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2024-01-11	criteria provided, single submitter	clinical testing