TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15131	45616;45617;45618	chr2:178621327;178621326;178621325	chr2:179486054;179486053;179486052
N2AB	13490	40693;40694;40695	chr2:178621327;178621326;178621325	chr2:179486054;179486053;179486052
N2A	12563	37912;37913;37914	chr2:178621327;178621326;178621325	chr2:179486054;179486053;179486052
N2B	6066	18421;18422;18423	chr2:178621327;178621326;178621325	chr2:179486054;179486053;179486052
Novex-1	6191	18796;18797;18798	chr2:178621327;178621326;178621325	chr2:179486054;179486053;179486052
Novex-2	6258	18997;18998;18999	chr2:178621327;178621326;178621325	chr2:179486054;179486053;179486052
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-103
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2351
• 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
I/V	None	None	None	N	0.119	0.186	0.300449992093	gnomAD-4.0.0	4.78689E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.59126E-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	0.5548	ambiguous	0.5427	ambiguous	-2.233	Highly Destabilizing	0.035	N	0.355	neutral	None	None	None	None	I
I/C	0.7554	likely_pathogenic	0.7708	pathogenic	-1.474	Destabilizing	0.824	D	0.454	neutral	None	None	None	None	I
I/D	0.9552	likely_pathogenic	0.9579	pathogenic	-1.955	Destabilizing	0.555	D	0.554	neutral	None	None	None	None	I
I/E	0.9109	likely_pathogenic	0.9177	pathogenic	-1.84	Destabilizing	0.555	D	0.555	neutral	None	None	None	None	I
I/F	0.3734	ambiguous	0.3945	ambiguous	-1.336	Destabilizing	0.38	N	0.443	neutral	None	None	None	None	I
I/G	0.8726	likely_pathogenic	0.8647	pathogenic	-2.673	Highly Destabilizing	0.262	N	0.531	neutral	None	None	None	None	I
I/H	0.8631	likely_pathogenic	0.8775	pathogenic	-1.902	Destabilizing	0.935	D	0.511	neutral	None	None	None	None	I
I/K	0.7449	likely_pathogenic	0.748	pathogenic	-1.562	Destabilizing	0.484	N	0.559	neutral	N	0.49915972	None	None	I
I/L	0.1731	likely_benign	0.1967	benign	-1.021	Destabilizing	0.005	N	0.266	neutral	N	0.490812596	None	None	I
I/M	0.1622	likely_benign	0.1737	benign	-0.931	Destabilizing	0.317	N	0.479	neutral	D	0.535856421	None	None	I
I/N	0.658	likely_pathogenic	0.6617	pathogenic	-1.569	Destabilizing	0.791	D	0.539	neutral	None	None	None	None	I
I/P	0.9804	likely_pathogenic	0.9807	pathogenic	-1.4	Destabilizing	0.555	D	0.554	neutral	None	None	None	None	I
I/Q	0.8135	likely_pathogenic	0.8298	pathogenic	-1.619	Destabilizing	0.791	D	0.539	neutral	None	None	None	None	I
I/R	0.6819	likely_pathogenic	0.6848	pathogenic	-1.097	Destabilizing	0.484	N	0.539	neutral	N	0.499339787	None	None	I
I/S	0.5995	likely_pathogenic	0.5891	pathogenic	-2.285	Highly Destabilizing	0.149	N	0.473	neutral	None	None	None	None	I
I/T	0.3647	ambiguous	0.3635	ambiguous	-2.047	Highly Destabilizing	0.062	N	0.386	neutral	N	0.451361076	None	None	I
I/V	0.0792	likely_benign	0.0764	benign	-1.4	Destabilizing	None	N	0.119	neutral	N	0.337114229	None	None	I
I/W	0.9593	likely_pathogenic	0.9642	pathogenic	-1.536	Destabilizing	0.935	D	0.553	neutral	None	None	None	None	I
I/Y	0.808	likely_pathogenic	0.8141	pathogenic	-1.299	Destabilizing	0.555	D	0.493	neutral	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.