TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23082	69469;69470;69471	chr2:178577091;178577090;178577089	chr2:179441818;179441817;179441816
N2AB	21441	64546;64547;64548	chr2:178577091;178577090;178577089	chr2:179441818;179441817;179441816
N2A	20514	61765;61766;61767	chr2:178577091;178577090;178577089	chr2:179441818;179441817;179441816
N2B	14017	42274;42275;42276	chr2:178577091;178577090;178577089	chr2:179441818;179441817;179441816
Novex-1	14142	42649;42650;42651	chr2:178577091;178577090;178577089	chr2:179441818;179441817;179441816
Novex-2	14209	42850;42851;42852	chr2:178577091;178577090;178577089	chr2:179441818;179441817;179441816
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: Fn3-55
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3672
• 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	0.976	N	0.557	0.367	0.408307896497	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	0.5019	ambiguous	0.3393	benign	-0.713	Destabilizing	0.958	D	0.511	neutral	N	0.49177499	None	None	N
T/C	0.9364	likely_pathogenic	0.8807	pathogenic	-0.487	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
T/D	0.9352	likely_pathogenic	0.9133	pathogenic	-0.004	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
T/E	0.9256	likely_pathogenic	0.8871	pathogenic	-0.026	Destabilizing	0.995	D	0.657	neutral	None	None	None	None	N
T/F	0.9545	likely_pathogenic	0.9202	pathogenic	-0.836	Destabilizing	0.991	D	0.721	prob.delet.	None	None	None	None	N
T/G	0.7557	likely_pathogenic	0.6949	pathogenic	-0.941	Destabilizing	0.995	D	0.641	neutral	None	None	None	None	N
T/H	0.9215	likely_pathogenic	0.8804	pathogenic	-1.16	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/I	0.8762	likely_pathogenic	0.7715	pathogenic	-0.206	Destabilizing	0.976	D	0.557	neutral	N	0.47081258	None	None	N
T/K	0.84	likely_pathogenic	0.7707	pathogenic	-0.68	Destabilizing	0.995	D	0.638	neutral	None	None	None	None	N
T/L	0.6342	likely_pathogenic	0.5033	ambiguous	-0.206	Destabilizing	0.086	N	0.338	neutral	None	None	None	None	N
T/M	0.4212	ambiguous	0.3043	benign	0.016	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	N
T/N	0.6451	likely_pathogenic	0.5529	ambiguous	-0.547	Destabilizing	0.998	D	0.667	neutral	N	0.477409172	None	None	N
T/P	0.7995	likely_pathogenic	0.6525	pathogenic	-0.343	Destabilizing	0.998	D	0.644	neutral	N	0.52073246	None	None	N
T/Q	0.8745	likely_pathogenic	0.7969	pathogenic	-0.74	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
T/R	0.8424	likely_pathogenic	0.7497	pathogenic	-0.396	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	N
T/S	0.4496	ambiguous	0.3431	ambiguous	-0.846	Destabilizing	0.979	D	0.527	neutral	N	0.49383386	None	None	N
T/V	0.7003	likely_pathogenic	0.5633	ambiguous	-0.343	Destabilizing	0.938	D	0.532	neutral	None	None	None	None	N
T/W	0.9884	likely_pathogenic	0.9781	pathogenic	-0.753	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/Y	0.9549	likely_pathogenic	0.9236	pathogenic	-0.531	Destabilizing	0.995	D	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.