TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14610	44053;44054;44055	chr2:178631220;178631219;178631218	chr2:179495947;179495946;179495945
N2AB	12969	39130;39131;39132	chr2:178631220;178631219;178631218	chr2:179495947;179495946;179495945
N2A	12042	36349;36350;36351	chr2:178631220;178631219;178631218	chr2:179495947;179495946;179495945
N2B	5545	16858;16859;16860	chr2:178631220;178631219;178631218	chr2:179495947;179495946;179495945
Novex-1	5670	17233;17234;17235	chr2:178631220;178631219;178631218	chr2:179495947;179495946;179495945
Novex-2	5737	17434;17435;17436	chr2:178631220;178631219;178631218	chr2:179495947;179495946;179495945
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-97
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3788
• 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
S/R	None	None	1.0	D	0.697	0.58	0.566666267248	gnomAD-4.0.0	1.36913E-06	None	None	None	None	N	None	2.98954E-05	0	None	0	0	None	0	0	8.99666E-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
S/A	0.3974	ambiguous	0.4889	ambiguous	-0.627	Destabilizing	0.998	D	0.367	neutral	None	None	None	None	N
S/C	0.6239	likely_pathogenic	0.7265	pathogenic	-0.363	Destabilizing	1.0	D	0.701	prob.neutral	D	0.696257136	None	None	N
S/D	0.9105	likely_pathogenic	0.9135	pathogenic	-0.237	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
S/E	0.9484	likely_pathogenic	0.9607	pathogenic	-0.198	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	N
S/F	0.9002	likely_pathogenic	0.9382	pathogenic	-0.563	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
S/G	0.4198	ambiguous	0.4788	ambiguous	-0.929	Destabilizing	0.999	D	0.434	neutral	D	0.638523603	None	None	N
S/H	0.9081	likely_pathogenic	0.9268	pathogenic	-1.31	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
S/I	0.8126	likely_pathogenic	0.8592	pathogenic	0.082	Stabilizing	1.0	D	0.726	prob.delet.	D	0.61819684	None	None	N
S/K	0.9889	likely_pathogenic	0.9928	pathogenic	-0.687	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	N
S/L	0.6102	likely_pathogenic	0.7158	pathogenic	0.082	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
S/M	0.8286	likely_pathogenic	0.866	pathogenic	0.202	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
S/N	0.6308	likely_pathogenic	0.595	pathogenic	-0.715	Destabilizing	0.999	D	0.508	neutral	D	0.546880022	None	None	N
S/P	0.9482	likely_pathogenic	0.9705	pathogenic	-0.118	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
S/Q	0.9467	likely_pathogenic	0.9635	pathogenic	-0.745	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
S/R	0.9673	likely_pathogenic	0.9811	pathogenic	-0.662	Destabilizing	1.0	D	0.697	prob.neutral	D	0.578021121	None	None	N
S/T	0.3772	ambiguous	0.3768	ambiguous	-0.678	Destabilizing	0.999	D	0.398	neutral	N	0.501916228	None	None	N
S/V	0.8398	likely_pathogenic	0.8712	pathogenic	-0.118	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
S/W	0.8947	likely_pathogenic	0.937	pathogenic	-0.617	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
S/Y	0.8235	likely_pathogenic	0.8793	pathogenic	-0.332	Destabilizing	1.0	D	0.755	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.