TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21156	63691;63692;63693	chr2:178587941;178587940;178587939	chr2:179452668;179452667;179452666
N2AB	19515	58768;58769;58770	chr2:178587941;178587940;178587939	chr2:179452668;179452667;179452666
N2A	18588	55987;55988;55989	chr2:178587941;178587940;178587939	chr2:179452668;179452667;179452666
N2B	12091	36496;36497;36498	chr2:178587941;178587940;178587939	chr2:179452668;179452667;179452666
Novex-1	12216	36871;36872;36873	chr2:178587941;178587940;178587939	chr2:179452668;179452667;179452666
Novex-2	12283	37072;37073;37074	chr2:178587941;178587940;178587939	chr2:179452668;179452667;179452666
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-41
• Domain position: 93
• Structural Position: 120
• Q(SASA): 0.3023
• 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
P/S	None	None	0.999	N	0.673	0.4	0.286465849087	gnomAD-4.0.0	1.60695E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44672E-05	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	0.1299	likely_benign	0.1272	benign	-1.503	Destabilizing	0.998	D	0.537	neutral	N	0.472506149	None	None	N
P/C	0.5964	likely_pathogenic	0.5999	pathogenic	-0.799	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/D	0.8181	likely_pathogenic	0.8124	pathogenic	-1.569	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
P/E	0.6736	likely_pathogenic	0.6663	pathogenic	-1.625	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
P/F	0.6079	likely_pathogenic	0.6349	pathogenic	-1.344	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/G	0.5379	ambiguous	0.5469	ambiguous	-1.758	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
P/H	0.3329	likely_benign	0.3436	ambiguous	-1.279	Destabilizing	0.434	N	0.51	neutral	N	0.482193841	None	None	N
P/I	0.6586	likely_pathogenic	0.6306	pathogenic	-0.917	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/K	0.7146	likely_pathogenic	0.706	pathogenic	-1.255	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
P/L	0.402	ambiguous	0.387	ambiguous	-0.917	Destabilizing	0.999	D	0.77	deleterious	N	0.505258392	None	None	N
P/M	0.6137	likely_pathogenic	0.61	pathogenic	-0.547	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/N	0.7034	likely_pathogenic	0.6985	pathogenic	-0.923	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
P/Q	0.4564	ambiguous	0.4581	ambiguous	-1.205	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/R	0.542	ambiguous	0.5323	ambiguous	-0.588	Destabilizing	0.999	D	0.747	deleterious	D	0.524883585	None	None	N
P/S	0.2812	likely_benign	0.2799	benign	-1.326	Destabilizing	0.999	D	0.673	neutral	N	0.494916045	None	None	N
P/T	0.3283	likely_benign	0.3105	benign	-1.294	Destabilizing	1.0	D	0.704	prob.neutral	N	0.484066719	None	None	N
P/V	0.4566	ambiguous	0.4311	ambiguous	-1.079	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
P/W	0.7269	likely_pathogenic	0.7436	pathogenic	-1.469	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/Y	0.5625	ambiguous	0.572	pathogenic	-1.233	Destabilizing	0.999	D	0.803	deleterious	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.