TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25611	77056;77057;77058	chr2:178569301;178569300;178569299	chr2:179434028;179434027;179434026
N2AB	23970	72133;72134;72135	chr2:178569301;178569300;178569299	chr2:179434028;179434027;179434026
N2A	23043	69352;69353;69354	chr2:178569301;178569300;178569299	chr2:179434028;179434027;179434026
N2B	16546	49861;49862;49863	chr2:178569301;178569300;178569299	chr2:179434028;179434027;179434026
Novex-1	16671	50236;50237;50238	chr2:178569301;178569300;178569299	chr2:179434028;179434027;179434026
Novex-2	16738	50437;50438;50439	chr2:178569301;178569300;178569299	chr2:179434028;179434027;179434026
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-74
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4154
• 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
T/R	None	None	0.001	N	0.15	0.218	0.393775345888	gnomAD-4.0.0	6.85287E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00461E-07	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	0.0788	likely_benign	0.0812	benign	-0.512	Destabilizing	0.001	N	0.069	neutral	N	0.520964533	None	None	N
T/C	0.2959	likely_benign	0.3464	ambiguous	-0.354	Destabilizing	0.951	D	0.353	neutral	None	None	None	None	N
T/D	0.4111	ambiguous	0.4577	ambiguous	0.145	Stabilizing	0.418	N	0.351	neutral	None	None	None	None	N
T/E	0.2742	likely_benign	0.3043	benign	0.084	Stabilizing	0.129	N	0.377	neutral	None	None	None	None	N
T/F	0.2434	likely_benign	0.2823	benign	-0.883	Destabilizing	0.836	D	0.377	neutral	None	None	None	None	N
T/G	0.1696	likely_benign	0.1889	benign	-0.676	Destabilizing	0.129	N	0.34	neutral	None	None	None	None	N
T/H	0.1775	likely_benign	0.209	benign	-0.973	Destabilizing	0.836	D	0.367	neutral	None	None	None	None	N
T/I	0.1328	likely_benign	0.1508	benign	-0.191	Destabilizing	0.351	N	0.421	neutral	N	0.518732305	None	None	N
T/K	0.1001	likely_benign	0.1213	benign	-0.474	Destabilizing	None	N	0.141	neutral	N	0.404369436	None	None	N
T/L	0.0867	likely_benign	0.0949	benign	-0.191	Destabilizing	0.129	N	0.361	neutral	None	None	None	None	N
T/M	0.0797	likely_benign	0.0814	benign	0.03	Stabilizing	0.94	D	0.372	neutral	None	None	None	None	N
T/N	0.1203	likely_benign	0.1278	benign	-0.288	Destabilizing	0.418	N	0.219	neutral	None	None	None	None	N
T/P	0.3674	ambiguous	0.4321	ambiguous	-0.268	Destabilizing	0.523	D	0.363	neutral	N	0.483071166	None	None	N
T/Q	0.142	likely_benign	0.161	benign	-0.523	Destabilizing	0.418	N	0.351	neutral	None	None	None	None	N
T/R	0.0978	likely_benign	0.1159	benign	-0.191	Destabilizing	0.001	N	0.15	neutral	N	0.503917568	None	None	N
T/S	0.0963	likely_benign	0.1009	benign	-0.54	Destabilizing	0.101	N	0.279	neutral	N	0.446829347	None	None	N
T/V	0.1047	likely_benign	0.115	benign	-0.268	Destabilizing	0.129	N	0.229	neutral	None	None	None	None	N
T/W	0.5066	ambiguous	0.5756	pathogenic	-0.839	Destabilizing	0.983	D	0.362	neutral	None	None	None	None	N
T/Y	0.2734	likely_benign	0.3173	benign	-0.582	Destabilizing	0.94	D	0.4	neutral	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.