TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5416	16471;16472;16473	chr2:178732930;178732929;178732928	chr2:179597657;179597656;179597655
N2AB	5099	15520;15521;15522	chr2:178732930;178732929;178732928	chr2:179597657;179597656;179597655
N2A	4172	12739;12740;12741	chr2:178732930;178732929;178732928	chr2:179597657;179597656;179597655
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-37
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0868
• 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/M	None	None	0.994	D	0.677	0.645	0.756989136078	gnomAD-4.0.0	2.05298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69854E-06	0	0
I/V	rs1283439535	-1.753	0.4	D	0.287	0.497	0.717175623165	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs1283439535	-1.753	0.4	D	0.287	0.497	0.717175623165	gnomAD-4.0.0	2.73729E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99509E-07	2.31873E-05	1.65706E-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
I/A	0.8453	likely_pathogenic	0.8516	pathogenic	-3.122	Highly Destabilizing	0.985	D	0.692	prob.neutral	None	None	None	None	N
I/C	0.876	likely_pathogenic	0.8812	pathogenic	-2.366	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
I/D	0.9809	likely_pathogenic	0.9795	pathogenic	-3.684	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
I/E	0.9696	likely_pathogenic	0.9677	pathogenic	-3.407	Highly Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
I/F	0.2718	likely_benign	0.2653	benign	-1.892	Destabilizing	0.994	D	0.699	prob.neutral	D	0.579453953	None	None	N
I/G	0.9487	likely_pathogenic	0.9437	pathogenic	-3.71	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
I/H	0.935	likely_pathogenic	0.9312	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/K	0.9129	likely_pathogenic	0.9012	pathogenic	-2.554	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
I/L	0.1646	likely_benign	0.1584	benign	-1.373	Destabilizing	0.061	N	0.305	neutral	D	0.554139082	None	None	N
I/M	0.1244	likely_benign	0.1164	benign	-1.352	Destabilizing	0.994	D	0.677	prob.neutral	D	0.589033424	None	None	N
I/N	0.8092	likely_pathogenic	0.7993	pathogenic	-3.071	Highly Destabilizing	0.999	D	0.868	deleterious	D	0.65313051	None	None	N
I/P	0.9877	likely_pathogenic	0.9864	pathogenic	-1.943	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
I/Q	0.9357	likely_pathogenic	0.9293	pathogenic	-2.859	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
I/R	0.8804	likely_pathogenic	0.8681	pathogenic	-2.251	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
I/S	0.8809	likely_pathogenic	0.8813	pathogenic	-3.742	Highly Destabilizing	0.997	D	0.813	deleterious	D	0.65313051	None	None	N
I/T	0.8821	likely_pathogenic	0.8874	pathogenic	-3.315	Highly Destabilizing	0.98	D	0.738	prob.delet.	D	0.62068818	None	None	N
I/V	0.1223	likely_benign	0.1344	benign	-1.943	Destabilizing	0.4	N	0.287	neutral	D	0.560811136	None	None	N
I/W	0.9089	likely_pathogenic	0.9049	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/Y	0.7246	likely_pathogenic	0.7125	pathogenic	-2.112	Highly Destabilizing	0.999	D	0.755	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.