TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21351	64276;64277;64278	chr2:178587160;178587159;178587158	chr2:179451887;179451886;179451885
N2AB	19710	59353;59354;59355	chr2:178587160;178587159;178587158	chr2:179451887;179451886;179451885
N2A	18783	56572;56573;56574	chr2:178587160;178587159;178587158	chr2:179451887;179451886;179451885
N2B	12286	37081;37082;37083	chr2:178587160;178587159;178587158	chr2:179451887;179451886;179451885
Novex-1	12411	37456;37457;37458	chr2:178587160;178587159;178587158	chr2:179451887;179451886;179451885
Novex-2	12478	37657;37658;37659	chr2:178587160;178587159;178587158	chr2:179451887;179451886;179451885
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-42
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3136
• 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/S	rs1421350004	-1.0	1.0	N	0.757	0.381	0.346992582518	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
P/S	rs1421350004	-1.0	1.0	N	0.757	0.381	0.346992582518	gnomAD-4.0.0	1.27384E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.71646E-05	0	6.0529E-05

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	0.0996	likely_benign	0.0928	benign	-1.143	Destabilizing	1.0	D	0.713	prob.delet.	N	0.484647193	None	None	N
P/C	0.5964	likely_pathogenic	0.5647	pathogenic	-0.793	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/D	0.9119	likely_pathogenic	0.8977	pathogenic	-0.967	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/E	0.7715	likely_pathogenic	0.7472	pathogenic	-1.066	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/F	0.6925	likely_pathogenic	0.6785	pathogenic	-1.244	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/G	0.4452	ambiguous	0.4353	ambiguous	-1.329	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/H	0.5121	ambiguous	0.4957	ambiguous	-0.77	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/I	0.6333	likely_pathogenic	0.6246	pathogenic	-0.776	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
P/K	0.8129	likely_pathogenic	0.7789	pathogenic	-0.812	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/L	0.3646	ambiguous	0.3641	ambiguous	-0.776	Destabilizing	1.0	D	0.773	deleterious	N	0.516994589	None	None	N
P/M	0.5614	ambiguous	0.5511	ambiguous	-0.504	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/N	0.7465	likely_pathogenic	0.731	pathogenic	-0.528	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/Q	0.4475	ambiguous	0.4154	ambiguous	-0.859	Destabilizing	1.0	D	0.771	deleterious	D	0.525352381	None	None	N
P/R	0.6655	likely_pathogenic	0.624	pathogenic	-0.157	Destabilizing	1.0	D	0.776	deleterious	D	0.536366292	None	None	N
P/S	0.2316	likely_benign	0.2157	benign	-0.946	Destabilizing	1.0	D	0.757	deleterious	N	0.482609731	None	None	N
P/T	0.2643	likely_benign	0.2531	benign	-0.951	Destabilizing	1.0	D	0.746	deleterious	N	0.513742586	None	None	N
P/V	0.439	ambiguous	0.4247	ambiguous	-0.864	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/W	0.8783	likely_pathogenic	0.8727	pathogenic	-1.27	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/Y	0.7318	likely_pathogenic	0.7182	pathogenic	-1.001	Destabilizing	1.0	D	0.805	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.