TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33583	100972;100973;100974	chr2:178536000;178535999;178535998	chr2:179400727;179400726;179400725
N2AB	31942	96049;96050;96051	chr2:178536000;178535999;178535998	chr2:179400727;179400726;179400725
N2A	31015	93268;93269;93270	chr2:178536000;178535999;178535998	chr2:179400727;179400726;179400725
N2B	24518	73777;73778;73779	chr2:178536000;178535999;178535998	chr2:179400727;179400726;179400725
Novex-1	24643	74152;74153;74154	chr2:178536000;178535999;178535998	chr2:179400727;179400726;179400725
Novex-2	24710	74353;74354;74355	chr2:178536000;178535999;178535998	chr2:179400727;179400726;179400725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-158
• Domain position: 88
• Structural Position: 172
• Q(SASA): 0.1169
• 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
A/D	None	None	1.0	D	0.87	0.618	0.68043841538	gnomAD-4.0.0	1.44632E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.40142E-05	1.75796E-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
A/C	0.6629	likely_pathogenic	0.7282	pathogenic	-1.252	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
A/D	0.9907	likely_pathogenic	0.9856	pathogenic	-1.208	Destabilizing	1.0	D	0.87	deleterious	D	0.548940134	None	None	N
A/E	0.9865	likely_pathogenic	0.9815	pathogenic	-1.219	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/F	0.932	likely_pathogenic	0.9187	pathogenic	-1.12	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
A/G	0.492	ambiguous	0.4119	ambiguous	-1.266	Destabilizing	0.998	D	0.657	neutral	D	0.530947533	None	None	N
A/H	0.9897	likely_pathogenic	0.9876	pathogenic	-1.377	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/I	0.633	likely_pathogenic	0.7447	pathogenic	-0.385	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
A/K	0.9952	likely_pathogenic	0.9931	pathogenic	-1.133	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/L	0.7096	likely_pathogenic	0.7294	pathogenic	-0.385	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
A/M	0.7654	likely_pathogenic	0.8099	pathogenic	-0.444	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/N	0.9688	likely_pathogenic	0.9669	pathogenic	-0.962	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/P	0.9938	likely_pathogenic	0.9929	pathogenic	-0.546	Destabilizing	1.0	D	0.864	deleterious	D	0.548940134	None	None	N
A/Q	0.9733	likely_pathogenic	0.9661	pathogenic	-1.105	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/R	0.985	likely_pathogenic	0.9766	pathogenic	-0.853	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/S	0.3124	likely_benign	0.3486	ambiguous	-1.391	Destabilizing	0.99	D	0.671	neutral	N	0.498866876	None	None	N
A/T	0.3221	likely_benign	0.4152	ambiguous	-1.295	Destabilizing	0.998	D	0.705	prob.neutral	D	0.538257507	None	None	N
A/V	0.2671	likely_benign	0.4042	ambiguous	-0.546	Destabilizing	0.987	D	0.407	neutral	D	0.534310338	None	None	N
A/W	0.9973	likely_pathogenic	0.9966	pathogenic	-1.433	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/Y	0.9824	likely_pathogenic	0.9778	pathogenic	-1.014	Destabilizing	1.0	D	0.887	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.