Submissions for variant NM_001267550.2(TTN):c.56970T>C (p.Pro18990=)

gnomAD frequency: 0.00113  dbSNP: rs372019333

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152288	SCV000201145	likely benign	not specified	2015-10-22	criteria provided, single submitter	clinical testing	p.Pro16422Pro in exon 241 of TTN: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.4% (35/9782) o f African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs372019333).
GeneDx	RCV000152288	SCV000236663	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)	RCV000152288	SCV000335301	likely benign	not specified	2015-09-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081047	SCV000555528	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617550	SCV000736828	likely benign	Cardiovascular phenotype	2017-04-25	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.
Athena Diagnostics	RCV000472628	SCV001146440	benign	not provided	2019-06-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001133744	SCV001293455	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	RCV001135231	SCV001295005	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-10-29	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	RCV001135232	SCV001295006	likely benign	Dilated cardiomyopathy 1G	2017-10-29	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	RCV001135233	SCV001295007	benign	Tibial muscular dystrophy	2017-10-29	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	RCV001135234	SCV001295008	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	RCV001170374	SCV001332948	benign	Cardiomyopathy	2018-03-29	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000152288	SCV001920830	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000472628	SCV001975671	likely benign	not provided		no assertion criteria provided	clinical testing