TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24553	73882;73883;73884	chr2:178572475;178572474;178572473	chr2:179437202;179437201;179437200
N2AB	22912	68959;68960;68961	chr2:178572475;178572474;178572473	chr2:179437202;179437201;179437200
N2A	21985	66178;66179;66180	chr2:178572475;178572474;178572473	chr2:179437202;179437201;179437200
N2B	15488	46687;46688;46689	chr2:178572475;178572474;178572473	chr2:179437202;179437201;179437200
Novex-1	15613	47062;47063;47064	chr2:178572475;178572474;178572473	chr2:179437202;179437201;179437200
Novex-2	15680	47263;47264;47265	chr2:178572475;178572474;178572473	chr2:179437202;179437201;179437200
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-66
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1158
• 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
N/K	rs1368527977	-0.313	0.999	N	0.525	0.354	0.209622950755	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-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
N/A	0.7554	likely_pathogenic	0.6718	pathogenic	-0.787	Destabilizing	0.991	D	0.734	prob.delet.	None	None	None	None	N
N/C	0.5076	ambiguous	0.4536	ambiguous	-0.282	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
N/D	0.7258	likely_pathogenic	0.6221	pathogenic	-1.836	Destabilizing	0.996	D	0.493	neutral	N	0.476470893	None	None	N
N/E	0.9437	likely_pathogenic	0.912	pathogenic	-1.627	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	N
N/F	0.881	likely_pathogenic	0.8454	pathogenic	-0.331	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
N/G	0.528	ambiguous	0.4732	ambiguous	-1.177	Destabilizing	1.0	D	0.451	neutral	None	None	None	None	N
N/H	0.2169	likely_benign	0.1973	benign	-0.914	Destabilizing	0.807	D	0.371	neutral	N	0.462126874	None	None	N
N/I	0.9194	likely_pathogenic	0.8902	pathogenic	0.24	Stabilizing	1.0	D	0.897	deleterious	N	0.492132839	None	None	N
N/K	0.8737	likely_pathogenic	0.8498	pathogenic	-0.382	Destabilizing	0.999	D	0.525	neutral	N	0.519460237	None	None	N
N/L	0.8315	likely_pathogenic	0.7777	pathogenic	0.24	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
N/M	0.8427	likely_pathogenic	0.7901	pathogenic	0.532	Stabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
N/P	0.9965	likely_pathogenic	0.9955	pathogenic	-0.074	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
N/Q	0.8041	likely_pathogenic	0.7555	pathogenic	-1.004	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
N/R	0.846	likely_pathogenic	0.828	pathogenic	-0.64	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
N/S	0.2438	likely_benign	0.2004	benign	-1.248	Destabilizing	0.996	D	0.468	neutral	N	0.473669232	None	None	N
N/T	0.6295	likely_pathogenic	0.5539	ambiguous	-0.865	Destabilizing	0.997	D	0.539	neutral	N	0.473584057	None	None	N
N/V	0.8883	likely_pathogenic	0.8558	pathogenic	-0.074	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
N/W	0.9555	likely_pathogenic	0.9431	pathogenic	-0.348	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
N/Y	0.3782	ambiguous	0.3419	ambiguous	0.021	Stabilizing	1.0	D	0.865	deleterious	N	0.472445195	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.