TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14675	44248;44249;44250	chr2:178630935;178630934;178630933	chr2:179495662;179495661;179495660
N2AB	13034	39325;39326;39327	chr2:178630935;178630934;178630933	chr2:179495662;179495661;179495660
N2A	12107	36544;36545;36546	chr2:178630935;178630934;178630933	chr2:179495662;179495661;179495660
N2B	5610	17053;17054;17055	chr2:178630935;178630934;178630933	chr2:179495662;179495661;179495660
Novex-1	5735	17428;17429;17430	chr2:178630935;178630934;178630933	chr2:179495662;179495661;179495660
Novex-2	5802	17629;17630;17631	chr2:178630935;178630934;178630933	chr2:179495662;179495661;179495660
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-98
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5098
• 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
I/T	None	None	0.999	D	0.629	0.433	0.577140404891	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	None	0	0	0	0	0
I/V	rs1384628153	None	0.985	N	0.32	0.192	0.427368086475	gnomAD-4.0.0	2.0558E-06	None	None	None	None	N	None	0	0	None	3.83818E-05	0	None	0	0	1.80004E-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
I/A	0.9573	likely_pathogenic	0.9382	pathogenic	-1.338	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
I/C	0.9792	likely_pathogenic	0.9699	pathogenic	-0.906	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
I/D	0.991	likely_pathogenic	0.9862	pathogenic	-0.687	Destabilizing	0.999	D	0.664	prob.neutral	None	None	None	None	N
I/E	0.9747	likely_pathogenic	0.9633	pathogenic	-0.7	Destabilizing	0.999	D	0.667	prob.neutral	None	None	None	None	N
I/F	0.6433	likely_pathogenic	0.5638	ambiguous	-0.957	Destabilizing	0.999	D	0.617	neutral	D	0.565267949	None	None	N
I/G	0.9849	likely_pathogenic	0.9774	pathogenic	-1.63	Destabilizing	0.999	D	0.685	prob.delet.	None	None	None	None	N
I/H	0.9837	likely_pathogenic	0.9746	pathogenic	-0.858	Destabilizing	1.0	D	0.724	deleterious	None	None	None	None	N
I/K	0.9482	likely_pathogenic	0.9259	pathogenic	-0.955	Destabilizing	0.999	D	0.668	prob.neutral	None	None	None	None	N
I/L	0.4198	ambiguous	0.3677	ambiguous	-0.628	Destabilizing	0.985	D	0.376	neutral	N	0.439865128	None	None	N
I/M	0.3141	likely_benign	0.2694	benign	-0.565	Destabilizing	0.999	D	0.591	neutral	D	0.526525433	None	None	N
I/N	0.8943	likely_pathogenic	0.8488	pathogenic	-0.778	Destabilizing	0.999	D	0.73	deleterious	D	0.56339073	None	None	N
I/P	0.9662	likely_pathogenic	0.9426	pathogenic	-0.832	Destabilizing	0.999	D	0.73	deleterious	None	None	None	None	N
I/Q	0.9727	likely_pathogenic	0.9581	pathogenic	-0.925	Destabilizing	1.0	D	0.696	prob.delet.	None	None	None	None	N
I/R	0.941	likely_pathogenic	0.9126	pathogenic	-0.404	Destabilizing	0.999	D	0.731	deleterious	None	None	None	None	N
I/S	0.9537	likely_pathogenic	0.9325	pathogenic	-1.35	Destabilizing	0.999	D	0.616	neutral	D	0.555825307	None	None	N
I/T	0.9342	likely_pathogenic	0.9135	pathogenic	-1.239	Destabilizing	0.999	D	0.629	neutral	D	0.562204063	None	None	N
I/V	0.2323	likely_benign	0.2235	benign	-0.832	Destabilizing	0.985	D	0.32	neutral	N	0.443599022	None	None	N
I/W	0.9757	likely_pathogenic	0.966	pathogenic	-1.02	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
I/Y	0.922	likely_pathogenic	0.8934	pathogenic	-0.792	Destabilizing	0.999	D	0.603	neutral	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.