TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18999	57220;57221;57222	chr2:178598622;178598621;178598620	chr2:179463349;179463348;179463347
N2AB	17358	52297;52298;52299	chr2:178598622;178598621;178598620	chr2:179463349;179463348;179463347
N2A	16431	49516;49517;49518	chr2:178598622;178598621;178598620	chr2:179463349;179463348;179463347
N2B	9934	30025;30026;30027	chr2:178598622;178598621;178598620	chr2:179463349;179463348;179463347
Novex-1	10059	30400;30401;30402	chr2:178598622;178598621;178598620	chr2:179463349;179463348;179463347
Novex-2	10126	30601;30602;30603	chr2:178598622;178598621;178598620	chr2:179463349;179463348;179463347
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-26
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4974
• 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
D/H	rs2052422100	None	1.0	N	0.643	0.481	0.415438038341	gnomAD-4.0.0	6.88008E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0105E-07	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
D/A	0.8632	likely_pathogenic	0.9054	pathogenic	-0.48	Destabilizing	1.0	D	0.719	prob.delet.	N	0.500298473	None	None	N
D/C	0.9835	likely_pathogenic	0.9887	pathogenic	-0.206	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
D/E	0.7875	likely_pathogenic	0.8219	pathogenic	-0.542	Destabilizing	1.0	D	0.389	neutral	N	0.467473978	None	None	N
D/F	0.9812	likely_pathogenic	0.9873	pathogenic	-0.105	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
D/G	0.8148	likely_pathogenic	0.8603	pathogenic	-0.781	Destabilizing	1.0	D	0.729	prob.delet.	N	0.47450911	None	None	N
D/H	0.945	likely_pathogenic	0.9618	pathogenic	-0.207	Destabilizing	1.0	D	0.643	neutral	N	0.482297471	None	None	N
D/I	0.9782	likely_pathogenic	0.9855	pathogenic	0.298	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
D/K	0.978	likely_pathogenic	0.9821	pathogenic	-0.188	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
D/L	0.9583	likely_pathogenic	0.9699	pathogenic	0.298	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/M	0.9884	likely_pathogenic	0.992	pathogenic	0.556	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
D/N	0.5206	ambiguous	0.5737	pathogenic	-0.597	Destabilizing	1.0	D	0.635	neutral	N	0.508301881	None	None	N
D/P	0.9975	likely_pathogenic	0.9988	pathogenic	0.063	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
D/Q	0.9622	likely_pathogenic	0.9689	pathogenic	-0.483	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
D/R	0.97	likely_pathogenic	0.975	pathogenic	0.063	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/S	0.6859	likely_pathogenic	0.755	pathogenic	-0.774	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
D/T	0.9258	likely_pathogenic	0.9501	pathogenic	-0.531	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/V	0.9329	likely_pathogenic	0.9544	pathogenic	0.063	Stabilizing	1.0	D	0.747	deleterious	N	0.486625884	None	None	N
D/W	0.9964	likely_pathogenic	0.9978	pathogenic	0.097	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
D/Y	0.8978	likely_pathogenic	0.9273	pathogenic	0.137	Stabilizing	1.0	D	0.663	neutral	N	0.502870488	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.