TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13910	41953;41954;41955	chr2:178635596;178635595;178635594	chr2:179500323;179500322;179500321
N2AB	12269	37030;37031;37032	chr2:178635596;178635595;178635594	chr2:179500323;179500322;179500321
N2A	11342	34249;34250;34251	chr2:178635596;178635595;178635594	chr2:179500323;179500322;179500321
N2B	4845	14758;14759;14760	chr2:178635596;178635595;178635594	chr2:179500323;179500322;179500321
Novex-1	4970	15133;15134;15135	chr2:178635596;178635595;178635594	chr2:179500323;179500322;179500321
Novex-2	5037	15334;15335;15336	chr2:178635596;178635595;178635594	chr2:179500323;179500322;179500321
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-89
• Domain position: 35
• Structural Position: 52
• Q(SASA): 0.8346
• 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
Y/C	rs1469876306	None	0.985	N	0.345	0.23	0.394079506076	gnomAD-4.0.0	1.64326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94994E-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
Y/A	0.5541	ambiguous	0.4863	ambiguous	-0.435	Destabilizing	0.312	N	0.342	neutral	None	None	None	None	N
Y/C	0.3279	likely_benign	0.2642	benign	-0.008	Destabilizing	0.985	D	0.345	neutral	N	0.450066054	None	None	N
Y/D	0.2636	likely_benign	0.1928	benign	0.867	Stabilizing	None	N	0.141	neutral	N	0.407438814	None	None	N
Y/E	0.616	likely_pathogenic	0.5386	ambiguous	0.844	Stabilizing	0.002	N	0.131	neutral	None	None	None	None	N
Y/F	0.1467	likely_benign	0.1404	benign	-0.272	Destabilizing	0.837	D	0.392	neutral	N	0.450066054	None	None	N
Y/G	0.4354	ambiguous	0.3781	ambiguous	-0.576	Destabilizing	0.312	N	0.355	neutral	None	None	None	None	N
Y/H	0.4648	ambiguous	0.3605	ambiguous	0.344	Stabilizing	0.947	D	0.354	neutral	N	0.449075702	None	None	N
Y/I	0.67	likely_pathogenic	0.5961	pathogenic	-0.104	Destabilizing	0.691	D	0.425	neutral	None	None	None	None	N
Y/K	0.8002	likely_pathogenic	0.7078	pathogenic	0.201	Stabilizing	0.312	N	0.385	neutral	None	None	None	None	N
Y/L	0.5672	likely_pathogenic	0.5272	ambiguous	-0.104	Destabilizing	0.479	N	0.37	neutral	None	None	None	None	N
Y/M	0.665	likely_pathogenic	0.6187	pathogenic	-0.175	Destabilizing	0.96	D	0.343	neutral	None	None	None	None	N
Y/N	0.1893	likely_benign	0.1434	benign	-0.082	Destabilizing	0.146	N	0.359	neutral	N	0.434057231	None	None	N
Y/P	0.7095	likely_pathogenic	0.642	pathogenic	-0.197	Destabilizing	0.691	D	0.504	neutral	None	None	None	None	N
Y/Q	0.7164	likely_pathogenic	0.6352	pathogenic	0.017	Stabilizing	0.524	D	0.397	neutral	None	None	None	None	N
Y/R	0.6983	likely_pathogenic	0.6084	pathogenic	0.346	Stabilizing	0.524	D	0.469	neutral	None	None	None	None	N
Y/S	0.2519	likely_benign	0.2043	benign	-0.438	Destabilizing	0.255	N	0.334	neutral	N	0.444000561	None	None	N
Y/T	0.5014	ambiguous	0.4281	ambiguous	-0.376	Destabilizing	0.312	N	0.38	neutral	None	None	None	None	N
Y/V	0.5519	ambiguous	0.4907	ambiguous	-0.197	Destabilizing	0.691	D	0.382	neutral	None	None	None	None	N
Y/W	0.4951	ambiguous	0.459	ambiguous	-0.481	Destabilizing	0.989	D	0.377	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.