TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30590	91993;91994;91995	chr2:178550070;178550069;178550068	chr2:179414797;179414796;179414795
N2AB	28949	87070;87071;87072	chr2:178550070;178550069;178550068	chr2:179414797;179414796;179414795
N2A	28022	84289;84290;84291	chr2:178550070;178550069;178550068	chr2:179414797;179414796;179414795
N2B	21525	64798;64799;64800	chr2:178550070;178550069;178550068	chr2:179414797;179414796;179414795
Novex-1	21650	65173;65174;65175	chr2:178550070;178550069;178550068	chr2:179414797;179414796;179414795
Novex-2	21717	65374;65375;65376	chr2:178550070;178550069;178550068	chr2:179414797;179414796;179414795
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-149
• Domain position: 59
• Structural Position: 145
• Q(SASA): 0.4435
• 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
T/N	None	None	0.007	N	0.179	0.097	0.27132560031	gnomAD-4.0.0	1.20032E-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
T/A	0.0818	likely_benign	0.0809	benign	-0.631	Destabilizing	0.309	N	0.353	neutral	N	0.508777175	None	None	I
T/C	0.2708	likely_benign	0.2562	benign	-0.195	Destabilizing	0.996	D	0.43	neutral	None	None	None	None	I
T/D	0.2566	likely_benign	0.2783	benign	-0.173	Destabilizing	0.004	N	0.135	neutral	None	None	None	None	I
T/E	0.3115	likely_benign	0.3109	benign	-0.222	Destabilizing	0.373	N	0.385	neutral	None	None	None	None	I
T/F	0.2741	likely_benign	0.2763	benign	-0.928	Destabilizing	0.91	D	0.436	neutral	None	None	None	None	I
T/G	0.1221	likely_benign	0.1195	benign	-0.829	Destabilizing	0.373	N	0.41	neutral	None	None	None	None	I
T/H	0.2213	likely_benign	0.2269	benign	-1.173	Destabilizing	0.953	D	0.416	neutral	None	None	None	None	I
T/I	0.2292	likely_benign	0.2235	benign	-0.207	Destabilizing	0.007	N	0.216	neutral	N	0.514300425	None	None	I
T/K	0.1968	likely_benign	0.2049	benign	-0.585	Destabilizing	0.742	D	0.36	neutral	None	None	None	None	I
T/L	0.1073	likely_benign	0.1046	benign	-0.207	Destabilizing	0.373	N	0.385	neutral	None	None	None	None	I
T/M	0.1097	likely_benign	0.1125	benign	0.232	Stabilizing	0.91	D	0.435	neutral	None	None	None	None	I
T/N	0.0769	likely_benign	0.0784	benign	-0.358	Destabilizing	0.007	N	0.179	neutral	N	0.464871682	None	None	I
T/P	0.372	ambiguous	0.3516	ambiguous	-0.318	Destabilizing	0.939	D	0.449	neutral	N	0.510851384	None	None	I
T/Q	0.1977	likely_benign	0.1967	benign	-0.618	Destabilizing	0.91	D	0.47	neutral	None	None	None	None	I
T/R	0.189	likely_benign	0.1972	benign	-0.275	Destabilizing	0.91	D	0.465	neutral	None	None	None	None	I
T/S	0.0642	likely_benign	0.0629	benign	-0.598	Destabilizing	0.028	N	0.147	neutral	N	0.464698324	None	None	I
T/V	0.155	likely_benign	0.1537	benign	-0.318	Destabilizing	0.373	N	0.284	neutral	None	None	None	None	I
T/W	0.6324	likely_pathogenic	0.6379	pathogenic	-0.88	Destabilizing	0.996	D	0.511	neutral	None	None	None	None	I
T/Y	0.3008	likely_benign	0.2875	benign	-0.639	Destabilizing	0.984	D	0.433	neutral	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.