Submissions for variant NM_001267550.2(TTN):c.71881G>A (p.Val23961Ile)

gnomAD frequency: 0.00001  dbSNP: rs397517690

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040573	SCV000064264	uncertain significance	not specified	2012-11-20	criteria provided, single submitter	clinical testing	The Val21393Ile variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has not been identified in larg e and broad European American and African American populations by the NHLBI Exom e Sequencing Project (http://evs.gs.washington.edu/EVS/), though it remains poss ible that this variant is common in other populations. Valine (Val) is not conse rved at position 21393, as wallaby has an isoleucine (Ile; this variant) at this position. Additional computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the cli nical significance of this variant.
GeneDx	RCV000725281	SCV000237502	likely benign	not provided	2020-10-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000725281	SCV000335647	uncertain significance	not provided	2015-10-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088776	SCV001083801	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-11	criteria provided, single submitter	clinical testing
Genetics and Genomics Program, Sidra Medicine	RCV001293079	SCV001434062	likely benign	Primary dilated cardiomyopathy		criteria provided, single submitter	research
CeGaT Center for Human Genetics Tuebingen	RCV000725281	SCV002563625	likely benign	not provided	2022-07-01	criteria provided, single submitter	clinical testing	TTN: BP4
Ambry Genetics	RCV002326757	SCV002636013	likely benign	Cardiovascular phenotype	2019-12-27	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.