TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7481	22666;22667;22668	chr2:178722346;178722345;178722344	chr2:179587073;179587072;179587071
N2AB	7164	21715;21716;21717	chr2:178722346;178722345;178722344	chr2:179587073;179587072;179587071
N2A	6237	18934;18935;18936	chr2:178722346;178722345;178722344	chr2:179587073;179587072;179587071
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-59
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1304
• 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	0.898	N	0.507	0.288	0.413113201963	gnomAD-4.0.0	6.84444E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9968E-07	0	0
T/N	None	None	0.962	N	0.573	0.392	0.481616744073	gnomAD-4.0.0	1.36889E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79936E-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	0.1483	likely_benign	0.1417	benign	-1.042	Destabilizing	0.004	N	0.172	neutral	N	0.438391583	None	None	N
T/C	0.686	likely_pathogenic	0.6191	pathogenic	-1.41	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
T/D	0.9238	likely_pathogenic	0.9148	pathogenic	-2.724	Highly Destabilizing	0.906	D	0.615	neutral	None	None	None	None	N
T/E	0.8934	likely_pathogenic	0.8778	pathogenic	-2.547	Highly Destabilizing	0.998	D	0.567	neutral	None	None	None	None	N
T/F	0.816	likely_pathogenic	0.7679	pathogenic	-0.928	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
T/G	0.5117	ambiguous	0.4988	ambiguous	-1.336	Destabilizing	0.05	N	0.347	neutral	None	None	None	None	N
T/H	0.8799	likely_pathogenic	0.8612	pathogenic	-1.487	Destabilizing	0.997	D	0.552	neutral	None	None	None	None	N
T/I	0.5067	ambiguous	0.4547	ambiguous	-0.295	Destabilizing	0.898	D	0.507	neutral	N	0.491244633	None	None	N
T/K	0.8879	likely_pathogenic	0.8717	pathogenic	-0.852	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
T/L	0.2397	likely_benign	0.2227	benign	-0.295	Destabilizing	0.24	N	0.293	neutral	None	None	None	None	N
T/M	0.1355	likely_benign	0.1297	benign	-0.511	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
T/N	0.5278	ambiguous	0.5037	ambiguous	-1.694	Destabilizing	0.962	D	0.573	neutral	N	0.500936656	None	None	N
T/P	0.4538	ambiguous	0.4132	ambiguous	-0.518	Destabilizing	0.962	D	0.629	neutral	N	0.484313658	None	None	N
T/Q	0.839	likely_pathogenic	0.8197	pathogenic	-1.538	Destabilizing	0.987	D	0.611	neutral	None	None	None	None	N
T/R	0.8174	likely_pathogenic	0.8045	pathogenic	-0.937	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
T/S	0.2888	likely_benign	0.281	benign	-1.621	Destabilizing	0.193	N	0.473	neutral	D	0.528363013	None	None	N
T/V	0.3031	likely_benign	0.2802	benign	-0.518	Destabilizing	0.352	N	0.193	neutral	None	None	None	None	N
T/W	0.9513	likely_pathogenic	0.94	pathogenic	-1.287	Destabilizing	1.0	D	0.542	neutral	None	None	None	None	N
T/Y	0.871	likely_pathogenic	0.8413	pathogenic	-0.827	Destabilizing	1.0	D	0.612	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.