TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27482	82669;82670;82671	chr2:178563688;178563687;178563686	chr2:179428415;179428414;179428413
N2AB	25841	77746;77747;77748	chr2:178563688;178563687;178563686	chr2:179428415;179428414;179428413
N2A	24914	74965;74966;74967	chr2:178563688;178563687;178563686	chr2:179428415;179428414;179428413
N2B	18417	55474;55475;55476	chr2:178563688;178563687;178563686	chr2:179428415;179428414;179428413
Novex-1	18542	55849;55850;55851	chr2:178563688;178563687;178563686	chr2:179428415;179428414;179428413
Novex-2	18609	56050;56051;56052	chr2:178563688;178563687;178563686	chr2:179428415;179428414;179428413
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-88
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.3403
• 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/I	None	None	0.638	N	0.489	0.519	0.407767136052	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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	0.1275	likely_benign	0.1225	benign	-0.625	Destabilizing	0.002	N	0.185	neutral	N	0.520543246	None	None	N
T/C	0.5271	ambiguous	0.5151	ambiguous	-0.503	Destabilizing	0.947	D	0.489	neutral	None	None	None	None	N
T/D	0.6925	likely_pathogenic	0.6803	pathogenic	-1.255	Destabilizing	0.7	D	0.439	neutral	None	None	None	None	N
T/E	0.6591	likely_pathogenic	0.6559	pathogenic	-1.251	Destabilizing	0.539	D	0.43	neutral	None	None	None	None	N
T/F	0.5541	ambiguous	0.5412	ambiguous	-0.912	Destabilizing	0.826	D	0.602	neutral	None	None	None	None	N
T/G	0.2269	likely_benign	0.2133	benign	-0.868	Destabilizing	0.25	N	0.438	neutral	None	None	None	None	N
T/H	0.4762	ambiguous	0.4562	ambiguous	-1.326	Destabilizing	0.947	D	0.569	neutral	None	None	None	None	N
T/I	0.6865	likely_pathogenic	0.6845	pathogenic	-0.07	Destabilizing	0.638	D	0.489	neutral	N	0.508154088	None	None	N
T/K	0.4522	ambiguous	0.4294	ambiguous	-0.731	Destabilizing	0.539	D	0.441	neutral	None	None	None	None	N
T/L	0.2197	likely_benign	0.2071	benign	-0.07	Destabilizing	0.25	N	0.405	neutral	None	None	None	None	N
T/M	0.1599	likely_benign	0.1578	benign	0.415	Stabilizing	0.947	D	0.485	neutral	None	None	None	None	N
T/N	0.2121	likely_benign	0.2138	benign	-0.904	Destabilizing	0.468	N	0.469	neutral	N	0.474891185	None	None	N
T/P	0.7751	likely_pathogenic	0.7591	pathogenic	-0.224	Destabilizing	0.638	D	0.493	neutral	D	0.526258343	None	None	N
T/Q	0.3512	ambiguous	0.3405	ambiguous	-1.163	Destabilizing	0.7	D	0.495	neutral	None	None	None	None	N
T/R	0.3499	ambiguous	0.3208	benign	-0.452	Destabilizing	0.7	D	0.497	neutral	None	None	None	None	N
T/S	0.124	likely_benign	0.1254	benign	-0.982	Destabilizing	0.002	N	0.275	neutral	N	0.509592747	None	None	N
T/V	0.4448	ambiguous	0.4515	ambiguous	-0.224	Destabilizing	0.25	N	0.402	neutral	None	None	None	None	N
T/W	0.868	likely_pathogenic	0.8575	pathogenic	-0.944	Destabilizing	0.982	D	0.607	neutral	None	None	None	None	N
T/Y	0.6143	likely_pathogenic	0.6031	pathogenic	-0.62	Destabilizing	0.826	D	0.602	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.