TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15904	47935;47936;47937	chr2:178617375;178617374;178617373	chr2:179482102;179482101;179482100
N2AB	14263	43012;43013;43014	chr2:178617375;178617374;178617373	chr2:179482102;179482101;179482100
N2A	13336	40231;40232;40233	chr2:178617375;178617374;178617373	chr2:179482102;179482101;179482100
N2B	6839	20740;20741;20742	chr2:178617375;178617374;178617373	chr2:179482102;179482101;179482100
Novex-1	6964	21115;21116;21117	chr2:178617375;178617374;178617373	chr2:179482102;179482101;179482100
Novex-2	7031	21316;21317;21318	chr2:178617375;178617374;178617373	chr2:179482102;179482101;179482100
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-3
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.6669
• 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
D/G	None	None	1.0	N	0.58	0.513	0.333154297509	gnomAD-4.0.0	3.48457E-06	None	None	None	None	N	None	0	0	None	0	2.56253E-05	None	0	0	3.63026E-06	0	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
D/A	0.1402	likely_benign	0.1397	benign	-0.05	Destabilizing	1.0	D	0.641	neutral	N	0.469566108	None	None	N
D/C	0.571	likely_pathogenic	0.5585	ambiguous	-0.177	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
D/E	0.1076	likely_benign	0.11	benign	-0.107	Destabilizing	1.0	D	0.443	neutral	N	0.460817336	None	None	N
D/F	0.6111	likely_pathogenic	0.6246	pathogenic	-0.128	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
D/G	0.1019	likely_benign	0.1006	benign	-0.165	Destabilizing	1.0	D	0.58	neutral	N	0.466585155	None	None	N
D/H	0.2942	likely_benign	0.2859	benign	0.452	Stabilizing	1.0	D	0.635	neutral	D	0.566979477	None	None	N
D/I	0.3479	ambiguous	0.3501	ambiguous	0.189	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
D/K	0.2181	likely_benign	0.2128	benign	0.284	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
D/L	0.3154	likely_benign	0.3188	benign	0.189	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
D/M	0.5107	ambiguous	0.5175	ambiguous	-0.006	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/N	0.1009	likely_benign	0.1019	benign	0.192	Stabilizing	1.0	D	0.578	neutral	N	0.474694324	None	None	N
D/P	0.3946	ambiguous	0.4042	ambiguous	0.128	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
D/Q	0.2247	likely_benign	0.2187	benign	0.195	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	N
D/R	0.2952	likely_benign	0.2821	benign	0.541	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
D/S	0.1139	likely_benign	0.1164	benign	0.027	Stabilizing	1.0	D	0.577	neutral	None	None	None	None	N
D/T	0.1869	likely_benign	0.193	benign	0.12	Stabilizing	1.0	D	0.61	neutral	None	None	None	None	N
D/V	0.1873	likely_benign	0.1868	benign	0.128	Stabilizing	1.0	D	0.718	prob.delet.	N	0.46537685	None	None	N
D/W	0.7858	likely_pathogenic	0.7917	pathogenic	-0.081	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/Y	0.2367	likely_benign	0.2394	benign	0.093	Stabilizing	1.0	D	0.713	prob.delet.	N	0.501245665	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.