TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7313	22162;22163;22164	chr2:178723070;178723069;178723068	chr2:179587797;179587796;179587795
N2AB	6996	21211;21212;21213	chr2:178723070;178723069;178723068	chr2:179587797;179587796;179587795
N2A	6069	18430;18431;18432	chr2:178723070;178723069;178723068	chr2:179587797;179587796;179587795
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-57
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1411
• 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
C/Y	None	None	0.983	N	0.817	0.382	0.793123502946	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
C/A	0.4936	ambiguous	0.5493	ambiguous	-1.651	Destabilizing	0.415	N	0.583	neutral	None	None	None	None	I
C/D	0.902	likely_pathogenic	0.9232	pathogenic	0.05	Stabilizing	0.923	D	0.827	deleterious	None	None	None	None	I
C/E	0.9482	likely_pathogenic	0.9595	pathogenic	0.158	Stabilizing	0.923	D	0.831	deleterious	None	None	None	None	I
C/F	0.5732	likely_pathogenic	0.6144	pathogenic	-0.978	Destabilizing	0.949	D	0.815	deleterious	N	0.520028416	None	None	I
C/G	0.3159	likely_benign	0.3506	ambiguous	-1.962	Destabilizing	0.565	D	0.775	deleterious	N	0.513280466	None	None	I
C/H	0.8938	likely_pathogenic	0.9131	pathogenic	-1.891	Destabilizing	0.989	D	0.814	deleterious	None	None	None	None	I
C/I	0.7554	likely_pathogenic	0.7968	pathogenic	-0.852	Destabilizing	0.961	D	0.817	deleterious	None	None	None	None	I
C/K	0.9764	likely_pathogenic	0.9815	pathogenic	-0.706	Destabilizing	0.858	D	0.827	deleterious	None	None	None	None	I
C/L	0.7592	likely_pathogenic	0.7758	pathogenic	-0.852	Destabilizing	0.775	D	0.729	prob.delet.	None	None	None	None	I
C/M	0.8506	likely_pathogenic	0.8767	pathogenic	-0.005	Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	I
C/N	0.8481	likely_pathogenic	0.8729	pathogenic	-0.696	Destabilizing	0.858	D	0.83	deleterious	None	None	None	None	I
C/P	0.9908	likely_pathogenic	0.9916	pathogenic	-1.093	Destabilizing	0.961	D	0.846	deleterious	None	None	None	None	I
C/Q	0.9117	likely_pathogenic	0.9258	pathogenic	-0.568	Destabilizing	0.923	D	0.851	deleterious	None	None	None	None	I
C/R	0.8734	likely_pathogenic	0.8835	pathogenic	-0.641	Destabilizing	0.901	D	0.848	deleterious	N	0.512519997	None	None	I
C/S	0.3435	ambiguous	0.3981	ambiguous	-1.293	Destabilizing	0.014	N	0.453	neutral	N	0.458020281	None	None	I
C/T	0.5143	ambiguous	0.5813	pathogenic	-0.994	Destabilizing	0.633	D	0.725	prob.delet.	None	None	None	None	I
C/V	0.6463	likely_pathogenic	0.6874	pathogenic	-1.093	Destabilizing	0.775	D	0.777	deleterious	None	None	None	None	I
C/W	0.8772	likely_pathogenic	0.8976	pathogenic	-0.955	Destabilizing	0.995	D	0.785	deleterious	N	0.520788884	None	None	I
C/Y	0.7955	likely_pathogenic	0.8324	pathogenic	-0.937	Destabilizing	0.983	D	0.817	deleterious	N	0.520281905	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.