TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2603	8032;8033;8034	chr2:178773157;178773156;178773155	chr2:179637884;179637883;179637882
N2AB	2603	8032;8033;8034	chr2:178773157;178773156;178773155	chr2:179637884;179637883;179637882
N2A	2603	8032;8033;8034	chr2:178773157;178773156;178773155	chr2:179637884;179637883;179637882
N2B	2557	7894;7895;7896	chr2:178773157;178773156;178773155	chr2:179637884;179637883;179637882
Novex-1	2557	7894;7895;7896	chr2:178773157;178773156;178773155	chr2:179637884;179637883;179637882
Novex-2	2557	7894;7895;7896	chr2:178773157;178773156;178773155	chr2:179637884;179637883;179637882
Novex-3	2603	8032;8033;8034	chr2:178773157;178773156;178773155	chr2:179637884;179637883;179637882

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-15
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.1784
• 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
T/A	rs775528928	-1.499	None	N	0.269	0.082	0.218112801441	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
T/A	rs775528928	-1.499	None	N	0.269	0.082	0.218112801441	gnomAD-4.0.0	1.0263E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34905E-05	0	0
T/I	None	None	None	N	0.477	0.14	0.289098819767	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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
T/A	0.0936	likely_benign	0.103	benign	-1.494	Destabilizing	None	N	0.269	neutral	N	0.464095187	None	None	N
T/C	0.3102	likely_benign	0.3372	benign	-1.286	Destabilizing	0.356	N	0.728	prob.delet.	None	None	None	None	N
T/D	0.3662	ambiguous	0.3988	ambiguous	-2.048	Highly Destabilizing	0.072	N	0.781	deleterious	None	None	None	None	N
T/E	0.2907	likely_benign	0.3155	benign	-1.813	Destabilizing	0.072	N	0.76	deleterious	None	None	None	None	N
T/F	0.258	likely_benign	0.2794	benign	-1.083	Destabilizing	0.214	N	0.742	deleterious	None	None	None	None	N
T/G	0.3189	likely_benign	0.3433	ambiguous	-1.908	Destabilizing	0.038	N	0.739	prob.delet.	None	None	None	None	N
T/H	0.2383	likely_benign	0.2551	benign	-1.834	Destabilizing	0.864	D	0.708	prob.delet.	None	None	None	None	N
T/I	0.1193	likely_benign	0.1278	benign	-0.39	Destabilizing	None	N	0.477	neutral	N	0.477274633	None	None	N
T/K	0.2133	likely_benign	0.2286	benign	-0.697	Destabilizing	0.055	N	0.76	deleterious	N	0.462680123	None	None	N
T/L	0.1064	likely_benign	0.1158	benign	-0.39	Destabilizing	0.002	N	0.578	neutral	None	None	None	None	N
T/M	0.1037	likely_benign	0.1124	benign	-0.486	Destabilizing	0.003	N	0.557	neutral	None	None	None	None	N
T/N	0.1256	likely_benign	0.1322	benign	-1.54	Destabilizing	0.356	N	0.712	prob.delet.	None	None	None	None	N
T/P	0.742	likely_pathogenic	0.7316	pathogenic	-0.73	Destabilizing	0.171	N	0.778	deleterious	D	0.562109385	None	None	N
T/Q	0.2353	likely_benign	0.2602	benign	-1.283	Destabilizing	0.356	N	0.755	deleterious	None	None	None	None	N
T/R	0.1603	likely_benign	0.1722	benign	-0.897	Destabilizing	0.171	N	0.775	deleterious	N	0.454928432	None	None	N
T/S	0.1086	likely_benign	0.1179	benign	-1.757	Destabilizing	0.012	N	0.591	neutral	N	0.449652625	None	None	N
T/V	0.1057	likely_benign	0.1148	benign	-0.73	Destabilizing	None	N	0.29	neutral	None	None	None	None	N
T/W	0.5991	likely_pathogenic	0.625	pathogenic	-1.226	Destabilizing	0.864	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.2597	likely_benign	0.2753	benign	-0.862	Destabilizing	0.356	N	0.73	prob.delet.	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.