TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30422	91489;91490;91491	chr2:178551636;178551635;178551634	chr2:179416363;179416362;179416361
N2AB	28781	86566;86567;86568	chr2:178551636;178551635;178551634	chr2:179416363;179416362;179416361
N2A	27854	83785;83786;83787	chr2:178551636;178551635;178551634	chr2:179416363;179416362;179416361
N2B	21357	64294;64295;64296	chr2:178551636;178551635;178551634	chr2:179416363;179416362;179416361
Novex-1	21482	64669;64670;64671	chr2:178551636;178551635;178551634	chr2:179416363;179416362;179416361
Novex-2	21549	64870;64871;64872	chr2:178551636;178551635;178551634	chr2:179416363;179416362;179416361
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: Fn3-110
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6232
• Predicted PPI site: I

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	0.849	0.49	0.710313493133	gnomAD-4.0.0	1.40508E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.79921E-04	9.14843E-07	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	0.205	likely_benign	0.1697	benign	-0.28	Destabilizing	0.999	D	0.821	deleterious	N	0.492806586	None	None	I
P/C	0.8733	likely_pathogenic	0.8292	pathogenic	-0.675	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/D	0.9269	likely_pathogenic	0.89	pathogenic	-0.319	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
P/E	0.7897	likely_pathogenic	0.7093	pathogenic	-0.444	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/F	0.9006	likely_pathogenic	0.8525	pathogenic	-0.652	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/G	0.8072	likely_pathogenic	0.7521	pathogenic	-0.353	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	I
P/H	0.6663	likely_pathogenic	0.5702	pathogenic	0.047	Stabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
P/I	0.7133	likely_pathogenic	0.6166	pathogenic	-0.241	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
P/K	0.8191	likely_pathogenic	0.7465	pathogenic	-0.318	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
P/L	0.3857	ambiguous	0.3135	benign	-0.241	Destabilizing	1.0	D	0.849	deleterious	N	0.481858808	None	None	I
P/M	0.6862	likely_pathogenic	0.5999	pathogenic	-0.445	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
P/N	0.8401	likely_pathogenic	0.765	pathogenic	-0.076	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
P/Q	0.5287	ambiguous	0.4271	ambiguous	-0.319	Destabilizing	1.0	D	0.833	deleterious	N	0.497369397	None	None	I
P/R	0.6216	likely_pathogenic	0.539	ambiguous	0.163	Stabilizing	1.0	D	0.875	deleterious	N	0.491582499	None	None	I
P/S	0.4603	ambiguous	0.374	ambiguous	-0.382	Destabilizing	1.0	D	0.863	deleterious	N	0.514459694	None	None	I
P/T	0.3902	ambiguous	0.3072	benign	-0.415	Destabilizing	1.0	D	0.847	deleterious	N	0.514206204	None	None	I
P/V	0.5036	ambiguous	0.4117	ambiguous	-0.224	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
P/W	0.9601	likely_pathogenic	0.9395	pathogenic	-0.712	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
P/Y	0.8991	likely_pathogenic	0.8492	pathogenic	-0.42	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I

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.