TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15841	47746;47747;47748	chr2:178617830;178617829;178617828	chr2:179482557;179482556;179482555
N2AB	14200	42823;42824;42825	chr2:178617830;178617829;178617828	chr2:179482557;179482556;179482555
N2A	13273	40042;40043;40044	chr2:178617830;178617829;178617828	chr2:179482557;179482556;179482555
N2B	6776	20551;20552;20553	chr2:178617830;178617829;178617828	chr2:179482557;179482556;179482555
Novex-1	6901	20926;20927;20928	chr2:178617830;178617829;178617828	chr2:179482557;179482556;179482555
Novex-2	6968	21127;21128;21129	chr2:178617830;178617829;178617828	chr2:179482557;179482556;179482555
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-2
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.297
• Predicted PPI site: I

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
V/I	None	None	0.001	N	0.275	0.058	0.146414634003	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
V/A	0.1577	likely_benign	0.1391	benign	-1.227	Destabilizing	0.22	N	0.619	neutral	N	0.473554857	None	None	I
V/C	0.727	likely_pathogenic	0.6169	pathogenic	-0.959	Destabilizing	0.968	D	0.744	deleterious	None	None	None	None	I
V/D	0.3973	ambiguous	0.4297	ambiguous	-0.846	Destabilizing	0.331	N	0.787	deleterious	N	0.468347705	None	None	I
V/E	0.2897	likely_benign	0.2995	benign	-0.911	Destabilizing	0.011	N	0.509	neutral	None	None	None	None	I
V/F	0.1693	likely_benign	0.1607	benign	-1.114	Destabilizing	0.497	N	0.743	deleterious	N	0.473213667	None	None	I
V/G	0.2814	likely_benign	0.276	benign	-1.456	Destabilizing	0.667	D	0.793	deleterious	N	0.515584758	None	None	I
V/H	0.6256	likely_pathogenic	0.5681	pathogenic	-0.792	Destabilizing	0.968	D	0.818	deleterious	None	None	None	None	I
V/I	0.0706	likely_benign	0.0651	benign	-0.734	Destabilizing	0.001	N	0.275	neutral	N	0.456550824	None	None	I
V/K	0.4802	ambiguous	0.4934	ambiguous	-0.894	Destabilizing	0.567	D	0.765	deleterious	None	None	None	None	I
V/L	0.1872	likely_benign	0.1544	benign	-0.734	Destabilizing	0.02	N	0.574	neutral	N	0.460211709	None	None	I
V/M	0.1527	likely_benign	0.1324	benign	-0.585	Destabilizing	0.567	D	0.73	prob.delet.	None	None	None	None	I
V/N	0.2993	likely_benign	0.2636	benign	-0.651	Destabilizing	0.726	D	0.829	deleterious	None	None	None	None	I
V/P	0.4916	ambiguous	0.418	ambiguous	-0.863	Destabilizing	0.89	D	0.814	deleterious	None	None	None	None	I
V/Q	0.3717	ambiguous	0.3497	ambiguous	-0.93	Destabilizing	0.567	D	0.811	deleterious	None	None	None	None	I
V/R	0.423	ambiguous	0.431	ambiguous	-0.267	Destabilizing	0.567	D	0.827	deleterious	None	None	None	None	I
V/S	0.2167	likely_benign	0.1884	benign	-1.16	Destabilizing	0.567	D	0.758	deleterious	None	None	None	None	I
V/T	0.1422	likely_benign	0.1249	benign	-1.122	Destabilizing	0.272	N	0.686	prob.neutral	None	None	None	None	I
V/W	0.7612	likely_pathogenic	0.7337	pathogenic	-1.142	Destabilizing	0.968	D	0.8	deleterious	None	None	None	None	I
V/Y	0.5367	ambiguous	0.4891	ambiguous	-0.883	Destabilizing	0.726	D	0.747	deleterious	None	None	None	None	I

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.