TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22505	67738;67739;67740	chr2:178579684;178579683;178579682	chr2:179444411;179444410;179444409
N2AB	20864	62815;62816;62817	chr2:178579684;178579683;178579682	chr2:179444411;179444410;179444409
N2A	19937	60034;60035;60036	chr2:178579684;178579683;178579682	chr2:179444411;179444410;179444409
N2B	13440	40543;40544;40545	chr2:178579684;178579683;178579682	chr2:179444411;179444410;179444409
Novex-1	13565	40918;40919;40920	chr2:178579684;178579683;178579682	chr2:179444411;179444410;179444409
Novex-2	13632	41119;41120;41121	chr2:178579684;178579683;178579682	chr2:179444411;179444410;179444409
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-51
• Domain position: 55
• Structural Position: 88
• Q(SASA): 0.5285
• 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
S/R	None	None	0.175	N	0.26	0.216	0.233785782151	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
S/A	0.0906	likely_benign	0.0905	benign	-0.592	Destabilizing	0.025	N	0.123	neutral	None	None	None	None	I
S/C	0.0976	likely_benign	0.1148	benign	-0.368	Destabilizing	0.946	D	0.305	neutral	N	0.482399603	None	None	I
S/D	0.2249	likely_benign	0.316	benign	0.109	Stabilizing	0.055	N	0.167	neutral	None	None	None	None	I
S/E	0.3525	ambiguous	0.4431	ambiguous	0.184	Stabilizing	0.002	N	0.132	neutral	None	None	None	None	I
S/F	0.1964	likely_benign	0.226	benign	-0.865	Destabilizing	0.667	D	0.343	neutral	None	None	None	None	I
S/G	0.0819	likely_benign	0.0963	benign	-0.862	Destabilizing	None	N	0.103	neutral	N	0.460012075	None	None	I
S/H	0.183	likely_benign	0.2448	benign	-1.043	Destabilizing	0.497	N	0.313	neutral	None	None	None	None	I
S/I	0.1216	likely_benign	0.1524	benign	0.038	Stabilizing	0.096	N	0.291	neutral	N	0.498415748	None	None	I
S/K	0.4247	ambiguous	0.568	pathogenic	-0.071	Destabilizing	0.055	N	0.165	neutral	None	None	None	None	I
S/L	0.0996	likely_benign	0.1091	benign	0.038	Stabilizing	0.055	N	0.243	neutral	None	None	None	None	I
S/M	0.1651	likely_benign	0.1834	benign	-0.116	Destabilizing	0.667	D	0.31	neutral	None	None	None	None	I
S/N	0.0766	likely_benign	0.1011	benign	-0.343	Destabilizing	None	N	0.123	neutral	N	0.462588234	None	None	I
S/P	0.3505	ambiguous	0.432	ambiguous	-0.139	Destabilizing	0.364	N	0.335	neutral	None	None	None	None	I
S/Q	0.2984	likely_benign	0.3766	ambiguous	-0.272	Destabilizing	0.22	N	0.139	neutral	None	None	None	None	I
S/R	0.377	ambiguous	0.5328	ambiguous	-0.124	Destabilizing	0.175	N	0.26	neutral	N	0.486139884	None	None	I
S/T	0.0763	likely_benign	0.0793	benign	-0.315	Destabilizing	0.001	N	0.168	neutral	N	0.456718267	None	None	I
S/V	0.1346	likely_benign	0.1534	benign	-0.139	Destabilizing	0.004	N	0.219	neutral	None	None	None	None	I
S/W	0.3163	likely_benign	0.4029	ambiguous	-0.966	Destabilizing	0.958	D	0.329	neutral	None	None	None	None	I
S/Y	0.1569	likely_benign	0.1883	benign	-0.572	Destabilizing	0.859	D	0.341	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.