Submissions for variant NM_001267550.2(TTN):c.60524C>T (p.Pro20175Leu)

gnomAD frequency: 0.00001  dbSNP: rs771358314

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000223279	SCV000272711	uncertain significance	not specified	2015-06-03	criteria provided, single submitter	clinical testing	The p.Pro17607Leu variant in TTN has not been previously reported in individuals with cardiomyopathy but has been identified in 6/66700 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computa tional prediction tools and conservation analysis suggest that the p.Pro17607Leu variant may impact the protein, though this information is not predictive enoug h to determine pathogenicity. In summary, the clinical significance of the p.Pro 17607Leu variant is uncertain.
Invitae	RCV000462468	SCV000543133	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-07-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000734811	SCV000862983	uncertain significance	not provided	2018-08-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001131880	SCV001291524	uncertain significance	Dilated cardiomyopathy 1G	2018-02-02	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	RCV001131881	SCV001291525	benign	Tibial muscular dystrophy	2018-02-02	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001131882	SCV001291526	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2018-02-02	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001131883	SCV001291527	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2018-02-02	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	RCV001131884	SCV001291528	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-02-02	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.
Revvity Omics, Revvity	RCV000734811	SCV003825594	uncertain significance	not provided	2020-04-01	criteria provided, single submitter	clinical testing
New York Genome Center	RCV003335235	SCV004046506	uncertain significance	Dilated cardiomyopathy 1G; Hypertrophic cardiomyopathy 9	2023-02-10	criteria provided, single submitter	clinical testing