Submissions for variant NM_001267550.2(TTN):c.61138C>A (p.Leu20380Met)

gnomAD frequency: 0.00105  dbSNP: rs201167216

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152268	SCV000201112	likely benign	not specified	2015-10-22	criteria provided, single submitter	clinical testing	p.Leu17812Met in exon 253 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.4% (35/9634) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201167216).
GeneDx	RCV000152268	SCV000236667	benign	not specified	2014-10-07	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.
Eurofins Ntd Llc (ga)	RCV000152268	SCV000335312	likely benign	not specified	2015-09-10	criteria provided, single submitter	clinical testing
Invitae	RCV001085555	SCV000555312	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618661	SCV000736826	likely benign	Cardiovascular phenotype	2018-12-13	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.
Athena Diagnostics Inc	RCV000461956	SCV001146452	benign	not provided	2019-06-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001132661	SCV001292329	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-04-28	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	RCV001132662	SCV001292330	likely benign	Dilated cardiomyopathy 1G	2017-09-24	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001132663	SCV001292331	benign	Tibial muscular dystrophy	2017-09-24	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001132664	SCV001292332	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-09-24	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001136052	SCV001295870	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2017-04-28	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001171295	SCV001334018	benign	Cardiomyopathy	2018-03-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935281	SCV004756516	likely benign	TTN-related condition	2022-02-09	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	RCV000152268	SCV001923972	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000461956	SCV001969518	likely benign	not provided		no assertion criteria provided	clinical testing