TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20983	63172;63173;63174	chr2:178588778;178588777;178588776	chr2:179453505;179453504;179453503
N2AB	19342	58249;58250;58251	chr2:178588778;178588777;178588776	chr2:179453505;179453504;179453503
N2A	18415	55468;55469;55470	chr2:178588778;178588777;178588776	chr2:179453505;179453504;179453503
N2B	11918	35977;35978;35979	chr2:178588778;178588777;178588776	chr2:179453505;179453504;179453503
Novex-1	12043	36352;36353;36354	chr2:178588778;178588777;178588776	chr2:179453505;179453504;179453503
Novex-2	12110	36553;36554;36555	chr2:178588778;178588777;178588776	chr2:179453505;179453504;179453503
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-40
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3156
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/G	None	None	1.0	N	0.849	0.43	0.763021800361	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/L	rs878904625	-0.193	0.997	N	0.592	0.358	0.615873902259	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.2846	likely_benign	0.2301	benign	-1.83	Destabilizing	0.999	D	0.608	neutral	N	0.393592295	None	None	N
V/C	0.653	likely_pathogenic	0.6415	pathogenic	-1.314	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/D	0.7643	likely_pathogenic	0.7057	pathogenic	-2.396	Highly Destabilizing	1.0	D	0.892	deleterious	N	0.463876313	None	None	N
V/E	0.593	likely_pathogenic	0.5318	ambiguous	-2.263	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/F	0.2682	likely_benign	0.2417	benign	-1.135	Destabilizing	1.0	D	0.891	deleterious	N	0.49177499	None	None	N
V/G	0.4074	ambiguous	0.3265	benign	-2.273	Highly Destabilizing	1.0	D	0.849	deleterious	N	0.435324274	None	None	N
V/H	0.7577	likely_pathogenic	0.7016	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/I	0.0883	likely_benign	0.0794	benign	-0.637	Destabilizing	0.997	D	0.539	neutral	N	0.473189229	None	None	N
V/K	0.6924	likely_pathogenic	0.6276	pathogenic	-1.616	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/L	0.2868	likely_benign	0.2289	benign	-0.637	Destabilizing	0.997	D	0.592	neutral	N	0.444039758	None	None	N
V/M	0.1805	likely_benign	0.156	benign	-0.619	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/N	0.4862	ambiguous	0.403	ambiguous	-1.7	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/P	0.9831	likely_pathogenic	0.9747	pathogenic	-1.005	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/Q	0.5119	ambiguous	0.451	ambiguous	-1.687	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/R	0.6197	likely_pathogenic	0.5542	ambiguous	-1.286	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/S	0.2744	likely_benign	0.2203	benign	-2.224	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/T	0.228	likely_benign	0.1687	benign	-1.977	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
V/W	0.8987	likely_pathogenic	0.8805	pathogenic	-1.608	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/Y	0.6718	likely_pathogenic	0.6347	pathogenic	-1.237	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.