TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33484	100675;100676;100677	chr2:178536297;178536296;178536295	chr2:179401024;179401023;179401022
N2AB	31843	95752;95753;95754	chr2:178536297;178536296;178536295	chr2:179401024;179401023;179401022
N2A	30916	92971;92972;92973	chr2:178536297;178536296;178536295	chr2:179401024;179401023;179401022
N2B	24419	73480;73481;73482	chr2:178536297;178536296;178536295	chr2:179401024;179401023;179401022
Novex-1	24544	73855;73856;73857	chr2:178536297;178536296;178536295	chr2:179401024;179401023;179401022
Novex-2	24611	74056;74057;74058	chr2:178536297;178536296;178536295	chr2:179401024;179401023;179401022
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-131
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.3345
• 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/A	None	None	0.983	N	0.729	0.228	0.294206760003	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	0
P/R	rs1235877834	-0.204	0.999	N	0.922	0.411	0.443999229985	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24141E-04	0	None	0	0	None	0	None	0	0	0
P/R	rs1235877834	-0.204	0.999	N	0.922	0.411	0.443999229985	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
P/R	rs1235877834	-0.204	0.999	N	0.922	0.411	0.443999229985	gnomAD-4.0.0	7.68852E-06	None	None	None	None	N	None	1.01526E-04	0	None	0	0	None	0	0	0	0	0
P/S	rs772916996	-0.926	0.911	N	0.397	0.218	0.264081493735	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
P/S	rs772916996	-0.926	0.911	N	0.397	0.218	0.264081493735	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs772916996	-0.926	0.911	N	0.397	0.218	0.264081493735	gnomAD-4.0.0	3.84421E-06	None	None	None	None	N	None	3.38341E-05	0	None	0	0	None	0	0	2.39325E-06	0	0
P/T	rs772916996	None	0.995	N	0.832	0.317	0.335910606209	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs772916996	None	0.995	N	0.832	0.317	0.335910606209	gnomAD-4.0.0	6.57358E-06	None	None	None	None	N	None	2.41359E-05	0	None	0	0	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
P/A	0.0627	likely_benign	0.0529	benign	-1.14	Destabilizing	0.983	D	0.729	deleterious	N	0.501543693	None	None	N
P/C	0.4041	ambiguous	0.3061	benign	-0.805	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/D	0.496	ambiguous	0.4244	ambiguous	-0.878	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
P/E	0.3434	ambiguous	0.2984	benign	-0.94	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
P/F	0.4438	ambiguous	0.3688	ambiguous	-1.01	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/G	0.2607	likely_benign	0.219	benign	-1.378	Destabilizing	0.993	D	0.822	deleterious	None	None	None	None	N
P/H	0.2592	likely_benign	0.2146	benign	-0.859	Destabilizing	1.0	D	0.869	deleterious	N	0.484251892	None	None	N
P/I	0.2447	likely_benign	0.1995	benign	-0.623	Destabilizing	0.999	D	0.919	deleterious	None	None	None	None	N
P/K	0.3637	ambiguous	0.3265	benign	-0.965	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
P/L	0.1402	likely_benign	0.1252	benign	-0.623	Destabilizing	0.999	D	0.881	deleterious	N	0.516185071	None	None	N
P/M	0.2975	likely_benign	0.2349	benign	-0.491	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/N	0.3069	likely_benign	0.2374	benign	-0.681	Destabilizing	0.998	D	0.908	deleterious	None	None	None	None	N
P/Q	0.2083	likely_benign	0.1764	benign	-0.925	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
P/R	0.2635	likely_benign	0.251	benign	-0.374	Destabilizing	0.999	D	0.922	deleterious	N	0.487619253	None	None	N
P/S	0.1166	likely_benign	0.0954	benign	-1.131	Destabilizing	0.911	D	0.397	neutral	N	0.477437469	None	None	N
P/T	0.095	likely_benign	0.0818	benign	-1.092	Destabilizing	0.995	D	0.832	deleterious	N	0.516494502	None	None	N
P/V	0.1843	likely_benign	0.1458	benign	-0.759	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
P/W	0.7004	likely_pathogenic	0.6374	pathogenic	-1.106	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/Y	0.4583	ambiguous	0.3848	ambiguous	-0.839	Destabilizing	1.0	D	0.907	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.