TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6787	20584;20585;20586	chr2:178725963;178725962;178725961	chr2:179590690;179590689;179590688
N2AB	6470	19633;19634;19635	chr2:178725963;178725962;178725961	chr2:179590690;179590689;179590688
N2A	5543	16852;16853;16854	chr2:178725963;178725962;178725961	chr2:179590690;179590689;179590688
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-52
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.6642
• 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
T/I	None	None	0.998	N	0.671	0.389	0.619501705969	gnomAD-4.0.0	1.59677E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86788E-06	0	0
T/S	None	None	0.154	N	0.288	0.079	0.149567049428	gnomAD-4.0.0	2.05521E-06	None	None	None	None	I	None	8.9815E-05	0	None	0	0	None	0	0	0	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
T/A	0.28	likely_benign	0.2938	benign	-0.418	Destabilizing	0.492	N	0.546	neutral	D	0.534635625	None	None	I
T/C	0.8397	likely_pathogenic	0.8925	pathogenic	-0.568	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
T/D	0.7045	likely_pathogenic	0.7058	pathogenic	0.124	Stabilizing	0.985	D	0.608	neutral	None	None	None	None	I
T/E	0.6274	likely_pathogenic	0.6747	pathogenic	0.109	Stabilizing	0.996	D	0.617	neutral	None	None	None	None	I
T/F	0.4511	ambiguous	0.5864	pathogenic	-0.864	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
T/G	0.6763	likely_pathogenic	0.6858	pathogenic	-0.577	Destabilizing	0.994	D	0.647	neutral	None	None	None	None	I
T/H	0.4626	ambiguous	0.5497	ambiguous	-0.57	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
T/I	0.4419	ambiguous	0.5451	ambiguous	-0.105	Destabilizing	0.998	D	0.671	neutral	N	0.519591602	None	None	I
T/K	0.508	ambiguous	0.5884	pathogenic	-0.307	Destabilizing	0.996	D	0.613	neutral	D	0.530517884	None	None	I
T/L	0.2645	likely_benign	0.3246	benign	-0.105	Destabilizing	0.995	D	0.657	neutral	None	None	None	None	I
T/M	0.1661	likely_benign	0.2073	benign	-0.388	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
T/N	0.2511	likely_benign	0.2755	benign	-0.361	Destabilizing	0.985	D	0.625	neutral	None	None	None	None	I
T/P	0.6672	likely_pathogenic	0.6772	pathogenic	-0.181	Destabilizing	0.99	D	0.671	neutral	N	0.503369419	None	None	I
T/Q	0.4829	ambiguous	0.5346	ambiguous	-0.431	Destabilizing	0.997	D	0.664	neutral	None	None	None	None	I
T/R	0.4731	ambiguous	0.5749	pathogenic	-0.024	Destabilizing	0.999	D	0.663	neutral	D	0.533982264	None	None	I
T/S	0.1844	likely_benign	0.1733	benign	-0.573	Destabilizing	0.154	N	0.288	neutral	N	0.46793063	None	None	I
T/V	0.374	ambiguous	0.4554	ambiguous	-0.181	Destabilizing	0.992	D	0.645	neutral	None	None	None	None	I
T/W	0.8102	likely_pathogenic	0.8813	pathogenic	-0.952	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
T/Y	0.4812	ambiguous	0.6325	pathogenic	-0.616	Destabilizing	1.0	D	0.709	prob.delet.	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.