TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32654	98185;98186;98187	chr2:178540206;178540205;178540204	chr2:179404933;179404932;179404931
N2AB	31013	93262;93263;93264	chr2:178540206;178540205;178540204	chr2:179404933;179404932;179404931
N2A	30086	90481;90482;90483	chr2:178540206;178540205;178540204	chr2:179404933;179404932;179404931
N2B	23589	70990;70991;70992	chr2:178540206;178540205;178540204	chr2:179404933;179404932;179404931
Novex-1	23714	71365;71366;71367	chr2:178540206;178540205;178540204	chr2:179404933;179404932;179404931
Novex-2	23781	71566;71567;71568	chr2:178540206;178540205;178540204	chr2:179404933;179404932;179404931
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-126
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.256
• 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/L	None	None	1.0	N	0.878	0.424	0.7065162276	gnomAD-4.0.0	1.5912E-06	None	None	None	None	N	None	5.65611E-05	0	None	0	0	None	0	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	0.257	likely_benign	0.2816	benign	-0.918	Destabilizing	1.0	D	0.76	deleterious	N	0.475368029	None	None	N
P/C	0.9206	likely_pathogenic	0.9198	pathogenic	-0.731	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/D	0.9735	likely_pathogenic	0.9758	pathogenic	-0.622	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
P/E	0.8981	likely_pathogenic	0.9014	pathogenic	-0.717	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/F	0.9531	likely_pathogenic	0.9575	pathogenic	-1.087	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/G	0.8898	likely_pathogenic	0.8953	pathogenic	-1.103	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/H	0.8613	likely_pathogenic	0.8708	pathogenic	-0.672	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/I	0.8009	likely_pathogenic	0.7904	pathogenic	-0.559	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/K	0.923	likely_pathogenic	0.9234	pathogenic	-0.608	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/L	0.4806	ambiguous	0.5166	ambiguous	-0.559	Destabilizing	1.0	D	0.878	deleterious	N	0.466266676	None	None	N
P/M	0.7987	likely_pathogenic	0.7999	pathogenic	-0.34	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/N	0.927	likely_pathogenic	0.926	pathogenic	-0.333	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/Q	0.7689	likely_pathogenic	0.7737	pathogenic	-0.628	Destabilizing	1.0	D	0.847	deleterious	N	0.498462715	None	None	N
P/R	0.8369	likely_pathogenic	0.8486	pathogenic	-0.068	Destabilizing	1.0	D	0.884	deleterious	N	0.48526585	None	None	N
P/S	0.6665	likely_pathogenic	0.6969	pathogenic	-0.784	Destabilizing	1.0	D	0.823	deleterious	N	0.472659004	None	None	N
P/T	0.5877	likely_pathogenic	0.6157	pathogenic	-0.779	Destabilizing	1.0	D	0.819	deleterious	N	0.503397493	None	None	N
P/V	0.633	likely_pathogenic	0.6265	pathogenic	-0.643	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/W	0.9805	likely_pathogenic	0.9827	pathogenic	-1.149	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/Y	0.9395	likely_pathogenic	0.9413	pathogenic	-0.836	Destabilizing	1.0	D	0.887	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.