TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14271	43036;43037;43038	chr2:178633548;178633547;178633546	chr2:179498275;179498274;179498273
N2AB	12630	38113;38114;38115	chr2:178633548;178633547;178633546	chr2:179498275;179498274;179498273
N2A	11703	35332;35333;35334	chr2:178633548;178633547;178633546	chr2:179498275;179498274;179498273
N2B	5206	15841;15842;15843	chr2:178633548;178633547;178633546	chr2:179498275;179498274;179498273
Novex-1	5331	16216;16217;16218	chr2:178633548;178633547;178633546	chr2:179498275;179498274;179498273
Novex-2	5398	16417;16418;16419	chr2:178633548;178633547;178633546	chr2:179498275;179498274;179498273
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: Ig-93
• Domain position: 41
• Structural Position: 70
• Q(SASA): 0.4519
• 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	0.684	D	0.353	0.337	0.64185220107	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.0639	likely_benign	0.058	benign	-0.503	Destabilizing	0.001	N	0.115	neutral	N	0.494041351	None	None	N
P/C	0.609	likely_pathogenic	0.506	ambiguous	-0.781	Destabilizing	0.987	D	0.389	neutral	None	None	None	None	N
P/D	0.4054	ambiguous	0.345	ambiguous	-0.187	Destabilizing	0.742	D	0.357	neutral	None	None	None	None	N
P/E	0.3	likely_benign	0.2418	benign	-0.278	Destabilizing	0.742	D	0.275	neutral	None	None	None	None	N
P/F	0.5255	ambiguous	0.3883	ambiguous	-0.629	Destabilizing	0.953	D	0.405	neutral	None	None	None	None	N
P/G	0.2627	likely_benign	0.2628	benign	-0.644	Destabilizing	0.373	N	0.277	neutral	None	None	None	None	N
P/H	0.2431	likely_benign	0.1818	benign	-0.158	Destabilizing	0.994	D	0.369	neutral	D	0.637839969	None	None	N
P/I	0.3626	ambiguous	0.2372	benign	-0.273	Destabilizing	0.91	D	0.401	neutral	None	None	None	None	N
P/K	0.3281	likely_benign	0.2662	benign	-0.503	Destabilizing	0.742	D	0.273	neutral	None	None	None	None	N
P/L	0.1533	likely_benign	0.1082	benign	-0.273	Destabilizing	0.684	D	0.353	neutral	D	0.533365599	None	None	N
P/M	0.3881	ambiguous	0.287	benign	-0.471	Destabilizing	0.984	D	0.367	neutral	None	None	None	None	N
P/N	0.2945	likely_benign	0.2552	benign	-0.342	Destabilizing	0.91	D	0.381	neutral	None	None	None	None	N
P/Q	0.1779	likely_benign	0.1421	benign	-0.52	Destabilizing	0.91	D	0.373	neutral	None	None	None	None	N
P/R	0.2461	likely_benign	0.188	benign	-0.036	Destabilizing	0.884	D	0.379	neutral	D	0.533453912	None	None	N
P/S	0.1077	likely_benign	0.095	benign	-0.724	Destabilizing	0.028	N	0.185	neutral	N	0.502086567	None	None	N
P/T	0.1213	likely_benign	0.0873	benign	-0.707	Destabilizing	0.028	N	0.179	neutral	D	0.538164761	None	None	N
P/V	0.2362	likely_benign	0.1714	benign	-0.316	Destabilizing	0.59	D	0.323	neutral	None	None	None	None	N
P/W	0.7541	likely_pathogenic	0.6466	pathogenic	-0.719	Destabilizing	0.996	D	0.481	neutral	None	None	None	None	N
P/Y	0.486	ambiguous	0.3792	ambiguous	-0.431	Destabilizing	0.984	D	0.396	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.