TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24223	72892;72893;72894	chr2:178573465;178573464;178573463	chr2:179438192;179438191;179438190
N2AB	22582	67969;67970;67971	chr2:178573465;178573464;178573463	chr2:179438192;179438191;179438190
N2A	21655	65188;65189;65190	chr2:178573465;178573464;178573463	chr2:179438192;179438191;179438190
N2B	15158	45697;45698;45699	chr2:178573465;178573464;178573463	chr2:179438192;179438191;179438190
Novex-1	15283	46072;46073;46074	chr2:178573465;178573464;178573463	chr2:179438192;179438191;179438190
Novex-2	15350	46273;46274;46275	chr2:178573465;178573464;178573463	chr2:179438192;179438191;179438190
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: Fn3-64
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1076
• 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	rs760890661	-2.45	0.249	N	0.494	0.403	0.32306181527	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
P/S	rs760890661	-2.45	0.249	N	0.494	0.403	0.32306181527	gnomAD-4.0.0	2.6417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.52353E-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	0.3251	likely_benign	0.3351	benign	-1.481	Destabilizing	0.807	D	0.586	neutral	D	0.537809367	None	None	N
P/C	0.8762	likely_pathogenic	0.8942	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/D	0.9971	likely_pathogenic	0.9967	pathogenic	-3.387	Highly Destabilizing	0.964	D	0.655	prob.neutral	None	None	None	None	N
P/E	0.9911	likely_pathogenic	0.9892	pathogenic	-3.312	Highly Destabilizing	0.964	D	0.667	prob.neutral	None	None	None	None	N
P/F	0.9971	likely_pathogenic	0.9977	pathogenic	-1.046	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
P/G	0.9339	likely_pathogenic	0.9352	pathogenic	-1.812	Destabilizing	0.964	D	0.655	prob.neutral	None	None	None	None	N
P/H	0.9874	likely_pathogenic	0.9868	pathogenic	-1.311	Destabilizing	0.999	D	0.692	prob.delet.	D	0.561789425	None	None	N
P/I	0.962	likely_pathogenic	0.9614	pathogenic	-0.619	Destabilizing	0.995	D	0.788	deleterious	None	None	None	None	N
P/K	0.9942	likely_pathogenic	0.993	pathogenic	-1.521	Destabilizing	0.964	D	0.66	prob.neutral	None	None	None	None	N
P/L	0.8825	likely_pathogenic	0.8864	pathogenic	-0.619	Destabilizing	0.993	D	0.796	deleterious	D	0.55925453	None	None	N
P/M	0.973	likely_pathogenic	0.9764	pathogenic	-0.927	Destabilizing	1.0	D	0.69	prob.delet.	None	None	None	None	N
P/N	0.9952	likely_pathogenic	0.9943	pathogenic	-1.906	Destabilizing	0.99	D	0.687	prob.delet.	None	None	None	None	N
P/Q	0.9771	likely_pathogenic	0.9753	pathogenic	-2.029	Highly Destabilizing	0.995	D	0.706	prob.delet.	None	None	None	None	N
P/R	0.9801	likely_pathogenic	0.9764	pathogenic	-1.096	Destabilizing	0.993	D	0.704	prob.delet.	D	0.549672651	None	None	N
P/S	0.7593	likely_pathogenic	0.7482	pathogenic	-2.207	Highly Destabilizing	0.249	N	0.494	neutral	N	0.519958601	None	None	N
P/T	0.8191	likely_pathogenic	0.81	pathogenic	-2.028	Highly Destabilizing	0.91	D	0.633	neutral	D	0.549165672	None	None	N
P/V	0.8683	likely_pathogenic	0.8646	pathogenic	-0.879	Destabilizing	0.995	D	0.699	prob.delet.	None	None	None	None	N
P/W	0.999	likely_pathogenic	0.999	pathogenic	-1.439	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
P/Y	0.9977	likely_pathogenic	0.9978	pathogenic	-1.088	Destabilizing	0.998	D	0.776	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.