TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24832	74719;74720;74721	chr2:178571638;178571637;178571636	chr2:179436365;179436364;179436363
N2AB	23191	69796;69797;69798	chr2:178571638;178571637;178571636	chr2:179436365;179436364;179436363
N2A	22264	67015;67016;67017	chr2:178571638;178571637;178571636	chr2:179436365;179436364;179436363
N2B	15767	47524;47525;47526	chr2:178571638;178571637;178571636	chr2:179436365;179436364;179436363
Novex-1	15892	47899;47900;47901	chr2:178571638;178571637;178571636	chr2:179436365;179436364;179436363
Novex-2	15959	48100;48101;48102	chr2:178571638;178571637;178571636	chr2:179436365;179436364;179436363
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: Fn3-68
• Domain position: 25
• Structural Position: 26
• Q(SASA): 0.4702
• 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	1.0	N	0.858	0.466	0.468085328875	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	0.1023	likely_benign	0.0943	benign	-1.409	Destabilizing	1.0	D	0.821	deleterious	N	0.503418923	None	None	N
P/C	0.567	likely_pathogenic	0.523	ambiguous	-1.025	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/D	0.7342	likely_pathogenic	0.7106	pathogenic	-1.168	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/E	0.3838	ambiguous	0.351	ambiguous	-1.137	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/F	0.5733	likely_pathogenic	0.5434	ambiguous	-1.037	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/G	0.6069	likely_pathogenic	0.5676	pathogenic	-1.743	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/H	0.3419	ambiguous	0.3257	benign	-1.168	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/I	0.2434	likely_benign	0.2279	benign	-0.583	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/K	0.3621	ambiguous	0.3445	ambiguous	-1.203	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/L	0.1282	likely_benign	0.12	benign	-0.583	Destabilizing	1.0	D	0.88	deleterious	N	0.515675733	None	None	N
P/M	0.2868	likely_benign	0.2663	benign	-0.562	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/N	0.5601	ambiguous	0.5438	ambiguous	-1.063	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/Q	0.2303	likely_benign	0.2169	benign	-1.156	Destabilizing	1.0	D	0.889	deleterious	N	0.495685373	None	None	N
P/R	0.3226	likely_benign	0.3025	benign	-0.737	Destabilizing	1.0	D	0.897	deleterious	N	0.493861721	None	None	N
P/S	0.234	likely_benign	0.22	benign	-1.589	Destabilizing	1.0	D	0.858	deleterious	N	0.48636653	None	None	N
P/T	0.1701	likely_benign	0.16	benign	-1.429	Destabilizing	1.0	D	0.864	deleterious	N	0.515422243	None	None	N
P/V	0.1907	likely_benign	0.1767	benign	-0.824	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/W	0.842	likely_pathogenic	0.8149	pathogenic	-1.217	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/Y	0.6124	likely_pathogenic	0.5853	pathogenic	-0.922	Destabilizing	1.0	D	0.877	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.