TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22657	68194;68195;68196	chr2:178579061;178579060;178579059	chr2:179443788;179443787;179443786
N2AB	21016	63271;63272;63273	chr2:178579061;178579060;178579059	chr2:179443788;179443787;179443786
N2A	20089	60490;60491;60492	chr2:178579061;178579060;178579059	chr2:179443788;179443787;179443786
N2B	13592	40999;41000;41001	chr2:178579061;178579060;178579059	chr2:179443788;179443787;179443786
Novex-1	13717	41374;41375;41376	chr2:178579061;178579060;178579059	chr2:179443788;179443787;179443786
Novex-2	13784	41575;41576;41577	chr2:178579061;178579060;178579059	chr2:179443788;179443787;179443786
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-52
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.2691
• 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/I	None	None	1.0	N	0.741	0.503	0.540288329166	gnomAD-4.0.0	2.05324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-06	1.15945E-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	0.2643	likely_benign	0.2524	benign	-0.741	Destabilizing	0.999	D	0.504	neutral	D	0.52431427	None	None	N
T/C	0.653	likely_pathogenic	0.6652	pathogenic	-0.473	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
T/D	0.5629	ambiguous	0.5198	ambiguous	-1.243	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
T/E	0.7281	likely_pathogenic	0.7079	pathogenic	-1.18	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/F	0.6098	likely_pathogenic	0.5843	pathogenic	-0.54	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/G	0.3622	ambiguous	0.3492	ambiguous	-1.075	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
T/H	0.5118	ambiguous	0.4905	ambiguous	-1.427	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
T/I	0.7379	likely_pathogenic	0.7066	pathogenic	0.085	Stabilizing	1.0	D	0.741	deleterious	N	0.490214417	None	None	N
T/K	0.5739	likely_pathogenic	0.5489	ambiguous	-0.973	Destabilizing	1.0	D	0.758	deleterious	N	0.472564235	None	None	N
T/L	0.2728	likely_benign	0.2635	benign	0.085	Stabilizing	0.999	D	0.661	neutral	None	None	None	None	N
T/M	0.17	likely_benign	0.1697	benign	0.417	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
T/N	0.1947	likely_benign	0.1762	benign	-1.178	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/P	0.7718	likely_pathogenic	0.7593	pathogenic	-0.157	Destabilizing	1.0	D	0.723	prob.delet.	N	0.501570722	None	None	N
T/Q	0.527	ambiguous	0.5147	ambiguous	-1.225	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
T/R	0.5124	ambiguous	0.4983	ambiguous	-0.846	Destabilizing	1.0	D	0.727	prob.delet.	N	0.512481123	None	None	N
T/S	0.1375	likely_benign	0.1257	benign	-1.289	Destabilizing	0.999	D	0.529	neutral	N	0.486966603	None	None	N
T/V	0.5515	ambiguous	0.5295	ambiguous	-0.157	Destabilizing	0.999	D	0.602	neutral	None	None	None	None	N
T/W	0.8756	likely_pathogenic	0.8662	pathogenic	-0.633	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/Y	0.6504	likely_pathogenic	0.635	pathogenic	-0.363	Destabilizing	1.0	D	0.736	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.