TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8376	25351;25352;25353	chr2:178717748;178717747;178717746	chr2:179582475;179582474;179582473
N2AB	8059	24400;24401;24402	chr2:178717748;178717747;178717746	chr2:179582475;179582474;179582473
N2A	7132	21619;21620;21621	chr2:178717748;178717747;178717746	chr2:179582475;179582474;179582473
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-69
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.2909
• 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	rs375209098	-1.367	0.633	N	0.226	0.225	None	gnomAD-2.1.1	1.11539E-04	None	None	None	None	N	None	0	5.68E-05	None	0	0	None	0	None	4.01E-05	2.13398E-04	1.41884E-04
P/S	rs375209098	-1.367	0.633	N	0.226	0.225	None	gnomAD-3.1.2	1.11758E-04	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	9.43E-05	0	2.20556E-04	0	0
P/S	rs375209098	-1.367	0.633	N	0.226	0.225	None	gnomAD-4.0.0	1.22752E-04	None	None	None	None	N	None	1.33586E-05	3.33567E-05	None	0	0	None	3.13234E-05	0	1.61081E-04	0	4.80631E-05

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	0.1359	likely_benign	0.1246	benign	-1.069	Destabilizing	0.728	D	0.464	neutral	N	0.514950999	None	None	N
P/C	0.8067	likely_pathogenic	0.7971	pathogenic	-0.7	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
P/D	0.72	likely_pathogenic	0.7298	pathogenic	-0.514	Destabilizing	0.936	D	0.509	neutral	None	None	None	None	N
P/E	0.5617	ambiguous	0.5618	ambiguous	-0.531	Destabilizing	0.959	D	0.497	neutral	None	None	None	None	N
P/F	0.7965	likely_pathogenic	0.7912	pathogenic	-0.79	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
P/G	0.5316	ambiguous	0.5026	ambiguous	-1.35	Destabilizing	0.977	D	0.535	neutral	None	None	None	None	N
P/H	0.3719	ambiguous	0.3633	ambiguous	-0.76	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
P/I	0.681	likely_pathogenic	0.6953	pathogenic	-0.421	Destabilizing	0.997	D	0.707	prob.neutral	None	None	None	None	N
P/K	0.5826	likely_pathogenic	0.5721	pathogenic	-0.804	Destabilizing	0.995	D	0.479	neutral	None	None	None	None	N
P/L	0.2794	likely_benign	0.2748	benign	-0.421	Destabilizing	0.988	D	0.565	neutral	D	0.528728373	None	None	N
P/M	0.6559	likely_pathogenic	0.6494	pathogenic	-0.373	Destabilizing	0.942	D	0.425	neutral	None	None	None	None	N
P/N	0.5999	likely_pathogenic	0.5881	pathogenic	-0.595	Destabilizing	0.989	D	0.667	neutral	None	None	None	None	N
P/Q	0.321	likely_benign	0.306	benign	-0.747	Destabilizing	0.998	D	0.594	neutral	N	0.487463529	None	None	N
P/R	0.3218	likely_benign	0.3197	benign	-0.306	Destabilizing	0.999	D	0.687	prob.neutral	N	0.515644432	None	None	N
P/S	0.1976	likely_benign	0.1791	benign	-1.135	Destabilizing	0.633	D	0.226	neutral	N	0.468541132	None	None	N
P/T	0.2295	likely_benign	0.2177	benign	-1.037	Destabilizing	0.908	D	0.481	neutral	N	0.494882371	None	None	N
P/V	0.4858	ambiguous	0.4943	ambiguous	-0.6	Destabilizing	0.949	D	0.531	neutral	None	None	None	None	N
P/W	0.8578	likely_pathogenic	0.861	pathogenic	-0.935	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
P/Y	0.7571	likely_pathogenic	0.754	pathogenic	-0.639	Destabilizing	1.0	D	0.717	prob.delet.	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.