TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15768	47527;47528;47529	chr2:178618049;178618048;178618047	chr2:179482776;179482775;179482774
N2AB	14127	42604;42605;42606	chr2:178618049;178618048;178618047	chr2:179482776;179482775;179482774
N2A	13200	39823;39824;39825	chr2:178618049;178618048;178618047	chr2:179482776;179482775;179482774
N2B	6703	20332;20333;20334	chr2:178618049;178618048;178618047	chr2:179482776;179482775;179482774
Novex-1	6828	20707;20708;20709	chr2:178618049;178618048;178618047	chr2:179482776;179482775;179482774
Novex-2	6895	20908;20909;20910	chr2:178618049;178618048;178618047	chr2:179482776;179482775;179482774
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-2
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3529
• 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	None	None	0.454	N	0.277	0.15	0.202086224978	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

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	0.0854	likely_benign	0.0811	benign	-0.518	Destabilizing	0.454	N	0.277	neutral	N	0.477684889	None	None	N
T/C	0.3589	ambiguous	0.3119	benign	-0.253	Destabilizing	0.037	N	0.191	neutral	None	None	None	None	N
T/D	0.3309	likely_benign	0.3096	benign	0.188	Stabilizing	0.915	D	0.376	neutral	None	None	None	None	N
T/E	0.2367	likely_benign	0.2209	benign	0.114	Stabilizing	0.915	D	0.401	neutral	None	None	None	None	N
T/F	0.3032	likely_benign	0.2601	benign	-1.009	Destabilizing	0.949	D	0.443	neutral	None	None	None	None	N
T/G	0.195	likely_benign	0.177	benign	-0.653	Destabilizing	0.007	N	0.187	neutral	None	None	None	None	N
T/H	0.2341	likely_benign	0.2066	benign	-1.021	Destabilizing	0.998	D	0.402	neutral	None	None	None	None	N
T/I	0.1647	likely_benign	0.1497	benign	-0.277	Destabilizing	0.669	D	0.328	neutral	N	0.480190324	None	None	N
T/K	0.149	likely_benign	0.1363	benign	-0.367	Destabilizing	0.915	D	0.391	neutral	None	None	None	None	N
T/L	0.1227	likely_benign	0.1105	benign	-0.277	Destabilizing	0.525	D	0.379	neutral	None	None	None	None	N
T/M	0.1076	likely_benign	0.103	benign	0.042	Stabilizing	0.974	D	0.397	neutral	None	None	None	None	N
T/N	0.1248	likely_benign	0.1189	benign	-0.151	Destabilizing	0.891	D	0.369	neutral	N	0.486478914	None	None	N
T/P	0.2975	likely_benign	0.3123	benign	-0.329	Destabilizing	0.989	D	0.423	neutral	D	0.529672976	None	None	N
T/Q	0.1823	likely_benign	0.1701	benign	-0.41	Destabilizing	0.991	D	0.423	neutral	None	None	None	None	N
T/R	0.1354	likely_benign	0.1181	benign	-0.113	Destabilizing	0.974	D	0.425	neutral	None	None	None	None	N
T/S	0.1061	likely_benign	0.1	benign	-0.394	Destabilizing	0.625	D	0.325	neutral	N	0.451470568	None	None	N
T/V	0.129	likely_benign	0.1165	benign	-0.329	Destabilizing	0.016	N	0.129	neutral	None	None	None	None	N
T/W	0.6111	likely_pathogenic	0.5408	ambiguous	-0.971	Destabilizing	0.998	D	0.451	neutral	None	None	None	None	N
T/Y	0.3241	likely_benign	0.2717	benign	-0.7	Destabilizing	0.974	D	0.433	neutral	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.