TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21848	65767;65768;65769	chr2:178583640;178583639;178583638	chr2:179448367;179448366;179448365
N2AB	20207	60844;60845;60846	chr2:178583640;178583639;178583638	chr2:179448367;179448366;179448365
N2A	19280	58063;58064;58065	chr2:178583640;178583639;178583638	chr2:179448367;179448366;179448365
N2B	12783	38572;38573;38574	chr2:178583640;178583639;178583638	chr2:179448367;179448366;179448365
Novex-1	12908	38947;38948;38949	chr2:178583640;178583639;178583638	chr2:179448367;179448366;179448365
Novex-2	12975	39148;39149;39150	chr2:178583640;178583639;178583638	chr2:179448367;179448366;179448365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-46
• Domain position: 92
• Structural Position: 123
• Q(SASA): 0.1444
• 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
P/L	rs1559520585	None	0.001	N	0.609	0.277	0.245660935333	gnomAD-4.0.0	1.37214E-06	None	None	None	None	N	None	0	0	None	0	2.53846E-05	None	0	0	0	0	1.66168E-05
P/T	None	None	0.335	N	0.659	0.206	0.231873229951	gnomAD-4.0.0	1.59783E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8685E-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
P/A	0.0892	likely_benign	0.0759	benign	-1.804	Destabilizing	0.172	N	0.573	neutral	N	0.492908354	None	None	N
P/C	0.5674	likely_pathogenic	0.4456	ambiguous	-1.157	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	N
P/D	0.6715	likely_pathogenic	0.6081	pathogenic	-1.794	Destabilizing	0.4	N	0.643	neutral	None	None	None	None	N
P/E	0.4073	ambiguous	0.3327	benign	-1.771	Destabilizing	0.018	N	0.497	neutral	None	None	None	None	N
P/F	0.6469	likely_pathogenic	0.5134	ambiguous	-1.381	Destabilizing	0.824	D	0.753	deleterious	None	None	None	None	N
P/G	0.5008	ambiguous	0.4251	ambiguous	-2.152	Highly Destabilizing	0.4	N	0.683	prob.neutral	None	None	None	None	N
P/H	0.4185	ambiguous	0.3108	benign	-1.635	Destabilizing	0.988	D	0.773	deleterious	N	0.485154172	None	None	N
P/I	0.2744	likely_benign	0.1915	benign	-0.924	Destabilizing	0.4	N	0.678	prob.neutral	None	None	None	None	N
P/K	0.4671	ambiguous	0.3561	ambiguous	-1.395	Destabilizing	0.571	D	0.659	prob.neutral	None	None	None	None	N
P/L	0.1506	likely_benign	0.1082	benign	-0.924	Destabilizing	0.001	N	0.609	neutral	N	0.490849483	None	None	N
P/M	0.3723	ambiguous	0.2723	benign	-0.676	Destabilizing	0.824	D	0.757	deleterious	None	None	None	None	N
P/N	0.5454	ambiguous	0.4522	ambiguous	-1.213	Destabilizing	0.824	D	0.679	prob.neutral	None	None	None	None	N
P/Q	0.2966	likely_benign	0.2096	benign	-1.392	Destabilizing	0.824	D	0.679	prob.neutral	None	None	None	None	N
P/R	0.3612	ambiguous	0.2663	benign	-0.844	Destabilizing	0.779	D	0.685	prob.delet.	N	0.489420133	None	None	N
P/S	0.2141	likely_benign	0.173	benign	-1.759	Destabilizing	0.013	N	0.501	neutral	N	0.507549732	None	None	N
P/T	0.1551	likely_benign	0.1181	benign	-1.63	Destabilizing	0.335	N	0.659	prob.neutral	N	0.511955474	None	None	N
P/V	0.1892	likely_benign	0.1395	benign	-1.185	Destabilizing	0.4	N	0.648	neutral	None	None	None	None	N
P/W	0.8309	likely_pathogenic	0.7398	pathogenic	-1.586	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	N
P/Y	0.6344	likely_pathogenic	0.5166	ambiguous	-1.314	Destabilizing	0.966	D	0.783	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.