TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33681	101266;101267;101268	chr2:178535574;178535573;178535572	chr2:179400301;179400300;179400299
N2AB	32040	96343;96344;96345	chr2:178535574;178535573;178535572	chr2:179400301;179400300;179400299
N2A	31113	93562;93563;93564	chr2:178535574;178535573;178535572	chr2:179400301;179400300;179400299
N2B	24616	74071;74072;74073	chr2:178535574;178535573;178535572	chr2:179400301;179400300;179400299
Novex-1	24741	74446;74447;74448	chr2:178535574;178535573;178535572	chr2:179400301;179400300;179400299
Novex-2	24808	74647;74648;74649	chr2:178535574;178535573;178535572	chr2:179400301;179400300;179400299
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-159
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.2002
• 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
T/I	None	None	1.0	N	0.893	0.531	0.675958104092	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
T/A	0.3424	ambiguous	0.2526	benign	-0.389	Destabilizing	0.993	D	0.623	neutral	N	0.483010211	None	None	N
T/C	0.8873	likely_pathogenic	0.8369	pathogenic	-0.356	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
T/D	0.8981	likely_pathogenic	0.8399	pathogenic	0.362	Stabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
T/E	0.7651	likely_pathogenic	0.6546	pathogenic	0.326	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
T/F	0.8464	likely_pathogenic	0.7293	pathogenic	-0.747	Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
T/G	0.7992	likely_pathogenic	0.733	pathogenic	-0.567	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
T/H	0.7109	likely_pathogenic	0.6129	pathogenic	-0.771	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
T/I	0.5999	likely_pathogenic	0.4502	ambiguous	-0.032	Destabilizing	1.0	D	0.893	deleterious	N	0.494241613	None	None	N
T/K	0.5717	likely_pathogenic	0.4967	ambiguous	-0.337	Destabilizing	1.0	D	0.888	deleterious	N	0.482196836	None	None	N
T/L	0.404	ambiguous	0.3194	benign	-0.032	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/M	0.2365	likely_benign	0.1765	benign	-0.087	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
T/N	0.4825	ambiguous	0.3824	ambiguous	-0.248	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
T/P	0.5507	ambiguous	0.486	ambiguous	-0.12	Destabilizing	0.999	D	0.889	deleterious	N	0.509890332	None	None	N
T/Q	0.5392	ambiguous	0.4652	ambiguous	-0.366	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
T/R	0.4533	ambiguous	0.4134	ambiguous	-0.125	Destabilizing	1.0	D	0.893	deleterious	N	0.501367956	None	None	N
T/S	0.4769	ambiguous	0.3743	ambiguous	-0.484	Destabilizing	0.993	D	0.599	neutral	N	0.509969254	None	None	N
T/V	0.3993	ambiguous	0.3262	benign	-0.12	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
T/W	0.9341	likely_pathogenic	0.8885	pathogenic	-0.776	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
T/Y	0.8103	likely_pathogenic	0.6919	pathogenic	-0.477	Destabilizing	1.0	D	0.919	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.