TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20995	63208;63209;63210	chr2:178588742;178588741;178588740	chr2:179453469;179453468;179453467
N2AB	19354	58285;58286;58287	chr2:178588742;178588741;178588740	chr2:179453469;179453468;179453467
N2A	18427	55504;55505;55506	chr2:178588742;178588741;178588740	chr2:179453469;179453468;179453467
N2B	11930	36013;36014;36015	chr2:178588742;178588741;178588740	chr2:179453469;179453468;179453467
Novex-1	12055	36388;36389;36390	chr2:178588742;178588741;178588740	chr2:179453469;179453468;179453467
Novex-2	12122	36589;36590;36591	chr2:178588742;178588741;178588740	chr2:179453469;179453468;179453467
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-40
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1747
• 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
I/T	rs1275723419	None	0.822	N	0.779	0.492	0.712447893199	gnomAD-4.0.0	1.30036E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.70928E-05	0	0
I/V	rs1322917551	-1.512	0.006	N	0.241	0.123	0.469333501611	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	6.5189E-04	None	0	None	0	0	0
I/V	rs1322917551	-1.512	0.006	N	0.241	0.123	0.469333501611	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93949E-04	None	0	0	0	0	0
I/V	rs1322917551	-1.512	0.006	N	0.241	0.123	0.469333501611	gnomAD-4.0.0	6.57661E-06	None	None	None	None	N	None	0	0	None	0	1.93949E-04	None	0	0	0	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
I/A	0.9675	likely_pathogenic	0.9576	pathogenic	-2.075	Highly Destabilizing	0.754	D	0.652	neutral	None	None	None	None	N
I/C	0.9753	likely_pathogenic	0.9705	pathogenic	-1.176	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
I/D	0.9989	likely_pathogenic	0.9985	pathogenic	-1.568	Destabilizing	0.993	D	0.843	deleterious	None	None	None	None	N
I/E	0.9958	likely_pathogenic	0.9942	pathogenic	-1.542	Destabilizing	0.978	D	0.834	deleterious	None	None	None	None	N
I/F	0.9226	likely_pathogenic	0.9234	pathogenic	-1.557	Destabilizing	0.956	D	0.738	prob.delet.	None	None	None	None	N
I/G	0.9966	likely_pathogenic	0.9961	pathogenic	-2.438	Highly Destabilizing	0.978	D	0.832	deleterious	None	None	None	None	N
I/H	0.9964	likely_pathogenic	0.9956	pathogenic	-1.626	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
I/K	0.9888	likely_pathogenic	0.9863	pathogenic	-1.375	Destabilizing	0.971	D	0.832	deleterious	D	0.53499821	None	None	N
I/L	0.4406	ambiguous	0.485	ambiguous	-1.124	Destabilizing	0.294	N	0.447	neutral	N	0.478275454	None	None	N
I/M	0.6129	likely_pathogenic	0.6051	pathogenic	-0.753	Destabilizing	0.942	D	0.706	prob.neutral	D	0.527236302	None	None	N
I/N	0.9788	likely_pathogenic	0.9728	pathogenic	-1.201	Destabilizing	0.993	D	0.84	deleterious	None	None	None	None	N
I/P	0.9698	likely_pathogenic	0.9535	pathogenic	-1.412	Destabilizing	0.993	D	0.842	deleterious	None	None	None	None	N
I/Q	0.9937	likely_pathogenic	0.9915	pathogenic	-1.378	Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	N
I/R	0.9851	likely_pathogenic	0.98	pathogenic	-0.742	Destabilizing	0.971	D	0.841	deleterious	D	0.546354515	None	None	N
I/S	0.9809	likely_pathogenic	0.973	pathogenic	-1.857	Destabilizing	0.956	D	0.806	deleterious	None	None	None	None	N
I/T	0.9536	likely_pathogenic	0.937	pathogenic	-1.709	Destabilizing	0.822	D	0.779	deleterious	N	0.513664724	None	None	N
I/V	0.0877	likely_benign	0.0942	benign	-1.412	Destabilizing	0.006	N	0.241	neutral	N	0.4705385	None	None	N
I/W	0.9981	likely_pathogenic	0.9982	pathogenic	-1.647	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
I/Y	0.9903	likely_pathogenic	0.9888	pathogenic	-1.437	Destabilizing	0.978	D	0.804	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.