TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22925	68998;68999;69000	chr2:178577653;178577652;178577651	chr2:179442380;179442379;179442378
N2AB	21284	64075;64076;64077	chr2:178577653;178577652;178577651	chr2:179442380;179442379;179442378
N2A	20357	61294;61295;61296	chr2:178577653;178577652;178577651	chr2:179442380;179442379;179442378
N2B	13860	41803;41804;41805	chr2:178577653;178577652;178577651	chr2:179442380;179442379;179442378
Novex-1	13985	42178;42179;42180	chr2:178577653;178577652;178577651	chr2:179442380;179442379;179442378
Novex-2	14052	42379;42380;42381	chr2:178577653;178577652;178577651	chr2:179442380;179442379;179442378
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: Fn3-54
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.2337
• 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/V	None	None	0.025	N	0.292	0.087	0.463843524616	gnomAD-4.0.0	1.59295E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43451E-05	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	0.5839	likely_pathogenic	0.5845	pathogenic	-1.178	Destabilizing	0.559	D	0.649	neutral	None	None	None	None	N
I/C	0.7923	likely_pathogenic	0.806	pathogenic	-0.84	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
I/D	0.9196	likely_pathogenic	0.9092	pathogenic	-0.35	Destabilizing	0.956	D	0.845	deleterious	None	None	None	None	N
I/E	0.8406	likely_pathogenic	0.8311	pathogenic	-0.394	Destabilizing	0.956	D	0.841	deleterious	None	None	None	None	N
I/F	0.2085	likely_benign	0.2226	benign	-0.876	Destabilizing	0.97	D	0.725	prob.delet.	N	0.493295143	None	None	N
I/G	0.8667	likely_pathogenic	0.8612	pathogenic	-1.433	Destabilizing	0.956	D	0.822	deleterious	None	None	None	None	N
I/H	0.7865	likely_pathogenic	0.7822	pathogenic	-0.558	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
I/K	0.7822	likely_pathogenic	0.773	pathogenic	-0.693	Destabilizing	0.956	D	0.843	deleterious	None	None	None	None	N
I/L	0.132	likely_benign	0.1393	benign	-0.591	Destabilizing	0.294	N	0.407	neutral	N	0.482731432	None	None	N
I/M	0.1557	likely_benign	0.1614	benign	-0.528	Destabilizing	0.97	D	0.719	prob.delet.	N	0.482738317	None	None	N
I/N	0.6086	likely_pathogenic	0.5767	pathogenic	-0.481	Destabilizing	0.942	D	0.851	deleterious	N	0.506701467	None	None	N
I/P	0.9105	likely_pathogenic	0.9012	pathogenic	-0.753	Destabilizing	0.978	D	0.851	deleterious	None	None	None	None	N
I/Q	0.7523	likely_pathogenic	0.7518	pathogenic	-0.685	Destabilizing	0.978	D	0.854	deleterious	None	None	None	None	N
I/R	0.7155	likely_pathogenic	0.7077	pathogenic	-0.095	Destabilizing	0.956	D	0.851	deleterious	None	None	None	None	N
I/S	0.5878	likely_pathogenic	0.5561	ambiguous	-1.085	Destabilizing	0.698	D	0.787	deleterious	N	0.457219699	None	None	N
I/T	0.4711	ambiguous	0.4182	ambiguous	-1.01	Destabilizing	0.014	N	0.449	neutral	N	0.48096389	None	None	N
I/V	0.0722	likely_benign	0.0693	benign	-0.753	Destabilizing	0.025	N	0.292	neutral	N	0.458835852	None	None	N
I/W	0.8569	likely_pathogenic	0.8712	pathogenic	-0.867	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N
I/Y	0.6553	likely_pathogenic	0.6738	pathogenic	-0.647	Destabilizing	0.993	D	0.783	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.