TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33525	100798;100799;100800	chr2:178536174;178536173;178536172	chr2:179400901;179400900;179400899
N2AB	31884	95875;95876;95877	chr2:178536174;178536173;178536172	chr2:179400901;179400900;179400899
N2A	30957	93094;93095;93096	chr2:178536174;178536173;178536172	chr2:179400901;179400900;179400899
N2B	24460	73603;73604;73605	chr2:178536174;178536173;178536172	chr2:179400901;179400900;179400899
Novex-1	24585	73978;73979;73980	chr2:178536174;178536173;178536172	chr2:179400901;179400900;179400899
Novex-2	24652	74179;74180;74181	chr2:178536174;178536173;178536172	chr2:179400901;179400900;179400899
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: Ig-158
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1003
• 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	None	None	0.992	D	0.765	0.664	0.629215704067	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	0	0	0
P/S	None	None	0.992	D	0.765	0.664	0.629215704067	gnomAD-4.0.0	2.56307E-06	None	None	None	None	N	None	0	0	None	0	2.42589E-05	None	0	0	0	1.34045E-05	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	0.8439	likely_pathogenic	0.813	pathogenic	-1.682	Destabilizing	0.915	D	0.647	neutral	N	0.513166605	None	None	N
P/C	0.9872	likely_pathogenic	0.982	pathogenic	-1.139	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9992	pathogenic	-2.173	Highly Destabilizing	0.96	D	0.825	deleterious	None	None	None	None	N
P/E	0.9986	likely_pathogenic	0.9983	pathogenic	-2.163	Highly Destabilizing	0.975	D	0.819	deleterious	None	None	None	None	N
P/F	0.9992	likely_pathogenic	0.9993	pathogenic	-1.365	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/G	0.9873	likely_pathogenic	0.9825	pathogenic	-2.014	Highly Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
P/H	0.9982	likely_pathogenic	0.9978	pathogenic	-1.682	Destabilizing	1.0	D	0.744	deleterious	D	0.537400153	None	None	N
P/I	0.9858	likely_pathogenic	0.989	pathogenic	-0.848	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
P/K	0.9994	likely_pathogenic	0.9992	pathogenic	-1.386	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
P/L	0.9746	likely_pathogenic	0.9776	pathogenic	-0.848	Destabilizing	0.998	D	0.808	deleterious	D	0.529367848	None	None	N
P/M	0.9942	likely_pathogenic	0.9945	pathogenic	-0.6	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/N	0.9982	likely_pathogenic	0.9977	pathogenic	-1.238	Destabilizing	0.993	D	0.814	deleterious	None	None	None	None	N
P/Q	0.9974	likely_pathogenic	0.9968	pathogenic	-1.43	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
P/R	0.9979	likely_pathogenic	0.9974	pathogenic	-0.885	Destabilizing	0.999	D	0.825	deleterious	D	0.56339122	None	None	N
P/S	0.9856	likely_pathogenic	0.9806	pathogenic	-1.676	Destabilizing	0.992	D	0.765	deleterious	D	0.551527935	None	None	N
P/T	0.9769	likely_pathogenic	0.9742	pathogenic	-1.567	Destabilizing	0.192	N	0.425	neutral	D	0.52865074	None	None	N
P/V	0.9561	likely_pathogenic	0.9619	pathogenic	-1.094	Destabilizing	0.991	D	0.775	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.639	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/Y	0.9993	likely_pathogenic	0.9992	pathogenic	-1.343	Destabilizing	1.0	D	0.799	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.