TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32655	98188;98189;98190	chr2:178540203;178540202;178540201	chr2:179404930;179404929;179404928
N2AB	31014	93265;93266;93267	chr2:178540203;178540202;178540201	chr2:179404930;179404929;179404928
N2A	30087	90484;90485;90486	chr2:178540203;178540202;178540201	chr2:179404930;179404929;179404928
N2B	23590	70993;70994;70995	chr2:178540203;178540202;178540201	chr2:179404930;179404929;179404928
Novex-1	23715	71368;71369;71370	chr2:178540203;178540202;178540201	chr2:179404930;179404929;179404928
Novex-2	23782	71569;71570;71571	chr2:178540203;178540202;178540201	chr2:179404930;179404929;179404928
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-126
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.2156
• 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	0.898	N	0.502	0.254	0.152612264143	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	0.1087	likely_benign	0.1072	benign	-0.861	Destabilizing	0.898	D	0.502	neutral	N	0.452086025	None	None	N
T/C	0.4344	ambiguous	0.4144	ambiguous	-0.394	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/D	0.8408	likely_pathogenic	0.8309	pathogenic	-0.309	Destabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	N
T/E	0.7133	likely_pathogenic	0.6754	pathogenic	-0.157	Destabilizing	0.995	D	0.692	prob.neutral	None	None	None	None	N
T/F	0.6452	likely_pathogenic	0.5755	pathogenic	-0.647	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
T/G	0.4133	ambiguous	0.3943	ambiguous	-1.243	Destabilizing	0.966	D	0.629	neutral	None	None	None	None	N
T/H	0.6638	likely_pathogenic	0.6454	pathogenic	-1.284	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
T/I	0.3054	likely_benign	0.2522	benign	0.115	Stabilizing	0.997	D	0.766	deleterious	N	0.472154653	None	None	N
T/K	0.7286	likely_pathogenic	0.6802	pathogenic	-0.204	Destabilizing	0.995	D	0.7	prob.neutral	None	None	None	None	N
T/L	0.181	likely_benign	0.141	benign	0.115	Stabilizing	0.983	D	0.617	neutral	None	None	None	None	N
T/M	0.1586	likely_benign	0.1522	benign	0.092	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
T/N	0.3571	ambiguous	0.3517	ambiguous	-0.672	Destabilizing	0.993	D	0.693	prob.neutral	D	0.525484919	None	None	N
T/P	0.4957	ambiguous	0.4725	ambiguous	-0.178	Destabilizing	0.997	D	0.763	deleterious	N	0.509112744	None	None	N
T/Q	0.5334	ambiguous	0.4893	ambiguous	-0.516	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
T/R	0.6899	likely_pathogenic	0.6343	pathogenic	-0.332	Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	N
T/S	0.1908	likely_benign	0.1944	benign	-1.011	Destabilizing	0.362	N	0.389	neutral	N	0.482310145	None	None	N
T/V	0.1888	likely_benign	0.1522	benign	-0.178	Destabilizing	0.983	D	0.586	neutral	None	None	None	None	N
T/W	0.8897	likely_pathogenic	0.8705	pathogenic	-0.709	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/Y	0.6894	likely_pathogenic	0.6491	pathogenic	-0.346	Destabilizing	0.999	D	0.811	deleterious	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.