TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4723	14392;14393;14394	chr2:178738286;178738285;178738284	chr2:179603013;179603012;179603011
N2AB	4406	13441;13442;13443	chr2:178738286;178738285;178738284	chr2:179603013;179603012;179603011
N2A	3479	10660;10661;10662	chr2:178738286;178738285;178738284	chr2:179603013;179603012;179603011
N2B	4360	13303;13304;13305	chr2:178738286;178738285;178738284	chr2:179603013;179603012;179603011
Novex-1	4485	13678;13679;13680	chr2:178738286;178738285;178738284	chr2:179603013;179603012;179603011
Novex-2	4552	13879;13880;13881	chr2:178738286;178738285;178738284	chr2:179603013;179603012;179603011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-30
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1326
• 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	0.001	N	0.419	0.425	0.625221479056	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85896E-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	0.7735	likely_pathogenic	0.8419	pathogenic	-2.848	Highly Destabilizing	0.035	N	0.674	neutral	None	None	None	None	N
I/C	0.9062	likely_pathogenic	0.9413	pathogenic	-1.87	Destabilizing	0.824	D	0.761	deleterious	None	None	None	None	N
I/D	0.9912	likely_pathogenic	0.9943	pathogenic	-3.397	Highly Destabilizing	0.38	N	0.835	deleterious	None	None	None	None	N
I/E	0.9819	likely_pathogenic	0.9853	pathogenic	-3.131	Highly Destabilizing	0.38	N	0.817	deleterious	None	None	None	None	N
I/F	0.402	ambiguous	0.5315	ambiguous	-1.663	Destabilizing	0.317	N	0.755	deleterious	N	0.407056146	None	None	N
I/G	0.9472	likely_pathogenic	0.9681	pathogenic	-3.382	Highly Destabilizing	0.38	N	0.813	deleterious	None	None	None	None	N
I/H	0.9721	likely_pathogenic	0.9826	pathogenic	-2.887	Highly Destabilizing	0.935	D	0.821	deleterious	None	None	None	None	N
I/K	0.9726	likely_pathogenic	0.9796	pathogenic	-2.202	Highly Destabilizing	0.38	N	0.819	deleterious	None	None	None	None	N
I/L	0.2398	likely_benign	0.3224	benign	-1.26	Destabilizing	0.012	N	0.5	neutral	N	0.404445533	None	None	N
I/M	0.2175	likely_benign	0.2919	benign	-1.268	Destabilizing	0.317	N	0.689	prob.neutral	N	0.446886699	None	None	N
I/N	0.8869	likely_pathogenic	0.9125	pathogenic	-2.688	Highly Destabilizing	0.317	N	0.835	deleterious	N	0.447264385	None	None	N
I/P	0.9817	likely_pathogenic	0.9904	pathogenic	-1.779	Destabilizing	0.555	D	0.839	deleterious	None	None	None	None	N
I/Q	0.9675	likely_pathogenic	0.9777	pathogenic	-2.471	Highly Destabilizing	0.555	D	0.837	deleterious	None	None	None	None	N
I/R	0.9591	likely_pathogenic	0.971	pathogenic	-1.969	Destabilizing	0.555	D	0.841	deleterious	None	None	None	None	N
I/S	0.8099	likely_pathogenic	0.8705	pathogenic	-3.261	Highly Destabilizing	0.062	N	0.772	deleterious	N	0.447094376	None	None	N
I/T	0.6146	likely_pathogenic	0.7055	pathogenic	-2.865	Highly Destabilizing	0.001	N	0.419	neutral	N	0.446236162	None	None	N
I/V	0.097	likely_benign	0.1041	benign	-1.779	Destabilizing	None	N	0.19	neutral	N	0.413009723	None	None	N
I/W	0.9724	likely_pathogenic	0.9865	pathogenic	-2.101	Highly Destabilizing	0.935	D	0.815	deleterious	None	None	None	None	N
I/Y	0.8928	likely_pathogenic	0.9272	pathogenic	-1.881	Destabilizing	0.555	D	0.784	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.