TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26161	78706;78707;78708	chr2:178567651;178567650;178567649	chr2:179432378;179432377;179432376
N2AB	24520	73783;73784;73785	chr2:178567651;178567650;178567649	chr2:179432378;179432377;179432376
N2A	23593	71002;71003;71004	chr2:178567651;178567650;178567649	chr2:179432378;179432377;179432376
N2B	17096	51511;51512;51513	chr2:178567651;178567650;178567649	chr2:179432378;179432377;179432376
Novex-1	17221	51886;51887;51888	chr2:178567651;178567650;178567649	chr2:179432378;179432377;179432376
Novex-2	17288	52087;52088;52089	chr2:178567651;178567650;178567649	chr2:179432378;179432377;179432376
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-78
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1223
• 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
F/L	rs876658082	None	0.489	N	0.717	0.432	0.398283496042	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/L	rs876658082	None	0.489	N	0.717	0.432	0.398283496042	gnomAD-4.0.0	6.57462E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4705E-05	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
F/A	0.998	likely_pathogenic	0.998	pathogenic	-2.657	Highly Destabilizing	0.754	D	0.835	deleterious	None	None	None	None	N
F/C	0.9833	likely_pathogenic	0.9799	pathogenic	-1.513	Destabilizing	0.992	D	0.83	deleterious	D	0.567052436	None	None	N
F/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.679	Highly Destabilizing	0.993	D	0.844	deleterious	None	None	None	None	N
F/E	0.9998	likely_pathogenic	0.9998	pathogenic	-3.432	Highly Destabilizing	0.978	D	0.857	deleterious	None	None	None	None	N
F/G	0.998	likely_pathogenic	0.9982	pathogenic	-3.123	Highly Destabilizing	0.978	D	0.836	deleterious	None	None	None	None	N
F/H	0.9981	likely_pathogenic	0.9981	pathogenic	-2.258	Highly Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
F/I	0.9412	likely_pathogenic	0.9308	pathogenic	-1.113	Destabilizing	0.444	N	0.719	prob.delet.	N	0.507821239	None	None	N
F/K	0.9998	likely_pathogenic	0.9998	pathogenic	-2.291	Highly Destabilizing	0.978	D	0.857	deleterious	None	None	None	None	N
F/L	0.9911	likely_pathogenic	0.9901	pathogenic	-1.113	Destabilizing	0.489	N	0.717	prob.delet.	N	0.518140814	None	None	N
F/M	0.9717	likely_pathogenic	0.969	pathogenic	-0.808	Destabilizing	0.956	D	0.7	prob.neutral	None	None	None	None	N
F/N	0.9989	likely_pathogenic	0.999	pathogenic	-3.046	Highly Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	1.0	pathogenic	-1.645	Destabilizing	0.993	D	0.872	deleterious	None	None	None	None	N
F/Q	0.9997	likely_pathogenic	0.9997	pathogenic	-2.817	Highly Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
F/R	0.9994	likely_pathogenic	0.9995	pathogenic	-2.163	Highly Destabilizing	0.978	D	0.872	deleterious	None	None	None	None	N
F/S	0.9989	likely_pathogenic	0.9989	pathogenic	-3.433	Highly Destabilizing	0.942	D	0.836	deleterious	D	0.555531547	None	None	N
F/T	0.9988	likely_pathogenic	0.9988	pathogenic	-3.057	Highly Destabilizing	0.956	D	0.841	deleterious	None	None	None	None	N
F/V	0.9508	likely_pathogenic	0.9418	pathogenic	-1.645	Destabilizing	0.014	N	0.597	neutral	N	0.503360559	None	None	N
F/W	0.9657	likely_pathogenic	0.9618	pathogenic	-0.547	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
F/Y	0.6317	likely_pathogenic	0.5973	pathogenic	-0.955	Destabilizing	0.904	D	0.607	neutral	N	0.515586827	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.