Submissions for variant NM_004415.4(DSP):c.3650C>T (p.Thr1217Met)

gnomAD frequency: 0.00003  dbSNP: rs535202724

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150568	SCV000197821	benign	not specified	2019-07-26	criteria provided, single submitter	clinical testing	The p.Thr1217Met variant in DSP is classified as benign because it has been identified in 0.3% (83/30592) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein. ACMG/AMP Criteria applied: BA1, BP4.
Illumina Laboratory Services, Illumina	RCV000352140	SCV000465002	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000381164	SCV000465003	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000288923	SCV000465004	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.
Ambry Genetics	RCV000620762	SCV000737826	likely benign	Cardiovascular phenotype	2016-11-30	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000641836	SCV000763486	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-27	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777712	SCV000913655	likely benign	Cardiomyopathy	2018-10-10	criteria provided, single submitter	clinical testing
Genetics and Genomics Program, Sidra Medicine	RCV001293159	SCV001434156	likely benign	Primary dilated cardiomyopathy		criteria provided, single submitter	research
GeneDx	RCV001528379	SCV001792065	likely benign	not provided	2020-07-27	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24704780)
All of Us Research Program, National Institutes of Health	RCV003998200	SCV004822076	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2023-12-18	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528379	SCV001740039	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000150568	SCV001918517	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528379	SCV001932380	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528379	SCV001967796	likely benign	not provided		no assertion criteria provided	clinical testing