TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22243	66952;66953;66954	chr2:178581541;178581540;178581539	chr2:179446268;179446267;179446266
N2AB	20602	62029;62030;62031	chr2:178581541;178581540;178581539	chr2:179446268;179446267;179446266
N2A	19675	59248;59249;59250	chr2:178581541;178581540;178581539	chr2:179446268;179446267;179446266
N2B	13178	39757;39758;39759	chr2:178581541;178581540;178581539	chr2:179446268;179446267;179446266
Novex-1	13303	40132;40133;40134	chr2:178581541;178581540;178581539	chr2:179446268;179446267;179446266
Novex-2	13370	40333;40334;40335	chr2:178581541;178581540;178581539	chr2:179446268;179446267;179446266
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-49
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.2208
• 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
P/T	None	None	1.0	N	0.751	0.466	0.561180645722	gnomAD-4.0.0	4.79862E-06	None	None	None	None	I	None	0	0	None	0	0	None	5.66316E-05	0	0	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
P/A	0.1573	likely_benign	0.1541	benign	-1.577	Destabilizing	1.0	D	0.721	prob.delet.	N	0.463567197	None	None	I
P/C	0.8058	likely_pathogenic	0.8121	pathogenic	-0.85	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
P/D	0.9522	likely_pathogenic	0.9619	pathogenic	-1.268	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/E	0.8525	likely_pathogenic	0.8784	pathogenic	-1.282	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
P/F	0.8993	likely_pathogenic	0.9036	pathogenic	-1.278	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
P/G	0.7615	likely_pathogenic	0.7752	pathogenic	-1.883	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
P/H	0.6743	likely_pathogenic	0.6998	pathogenic	-1.363	Destabilizing	1.0	D	0.815	deleterious	N	0.48139519	None	None	I
P/I	0.8034	likely_pathogenic	0.8274	pathogenic	-0.835	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
P/K	0.8066	likely_pathogenic	0.845	pathogenic	-1.164	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/L	0.649	likely_pathogenic	0.7029	pathogenic	-0.835	Destabilizing	1.0	D	0.827	deleterious	N	0.507333351	None	None	I
P/M	0.8301	likely_pathogenic	0.852	pathogenic	-0.527	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
P/N	0.9166	likely_pathogenic	0.9265	pathogenic	-0.876	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
P/Q	0.6708	likely_pathogenic	0.7209	pathogenic	-1.085	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/R	0.6592	likely_pathogenic	0.7227	pathogenic	-0.602	Destabilizing	1.0	D	0.851	deleterious	N	0.491902122	None	None	I
P/S	0.4721	ambiguous	0.4936	ambiguous	-1.411	Destabilizing	1.0	D	0.757	deleterious	N	0.491395143	None	None	I
P/T	0.5323	ambiguous	0.5749	pathogenic	-1.321	Destabilizing	1.0	D	0.751	deleterious	N	0.512728628	None	None	I
P/V	0.658	likely_pathogenic	0.6912	pathogenic	-1.048	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/W	0.9552	likely_pathogenic	0.9646	pathogenic	-1.433	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
P/Y	0.9003	likely_pathogenic	0.9087	pathogenic	-1.167	Destabilizing	1.0	D	0.862	deleterious	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.