TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33519	100780;100781;100782	chr2:178536192;178536191;178536190	chr2:179400919;179400918;179400917
N2AB	31878	95857;95858;95859	chr2:178536192;178536191;178536190	chr2:179400919;179400918;179400917
N2A	30951	93076;93077;93078	chr2:178536192;178536191;178536190	chr2:179400919;179400918;179400917
N2B	24454	73585;73586;73587	chr2:178536192;178536191;178536190	chr2:179400919;179400918;179400917
Novex-1	24579	73960;73961;73962	chr2:178536192;178536191;178536190	chr2:179400919;179400918;179400917
Novex-2	24646	74161;74162;74163	chr2:178536192;178536191;178536190	chr2:179400919;179400918;179400917
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-158
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1158
• 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
V/L	None	None	0.381	D	0.673	0.378	0.485493271093	gnomAD-4.0.0	1.36873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79922E-06	0	0
V/M	None	None	0.994	D	0.727	0.548	0.688093782497	gnomAD-4.0.0	6.84367E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99609E-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
V/A	0.9526	likely_pathogenic	0.9304	pathogenic	-2.201	Highly Destabilizing	0.906	D	0.679	prob.neutral	N	0.466882985	None	None	N
V/C	0.9857	likely_pathogenic	0.9794	pathogenic	-1.685	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9984	pathogenic	-3.073	Highly Destabilizing	0.991	D	0.815	deleterious	None	None	None	None	N
V/E	0.9959	likely_pathogenic	0.9943	pathogenic	-2.887	Highly Destabilizing	0.052	N	0.558	neutral	D	0.601784633	None	None	N
V/F	0.8856	likely_pathogenic	0.8349	pathogenic	-1.177	Destabilizing	0.997	D	0.779	deleterious	None	None	None	None	N
V/G	0.9764	likely_pathogenic	0.9679	pathogenic	-2.68	Highly Destabilizing	0.996	D	0.812	deleterious	D	0.564406124	None	None	N
V/H	0.999	likely_pathogenic	0.9986	pathogenic	-2.446	Highly Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
V/I	0.1067	likely_benign	0.0898	benign	-0.85	Destabilizing	0.05	N	0.299	neutral	None	None	None	None	N
V/K	0.9978	likely_pathogenic	0.9967	pathogenic	-1.811	Destabilizing	0.975	D	0.797	deleterious	None	None	None	None	N
V/L	0.7915	likely_pathogenic	0.7058	pathogenic	-0.85	Destabilizing	0.381	N	0.673	neutral	D	0.535426621	None	None	N
V/M	0.7963	likely_pathogenic	0.7281	pathogenic	-0.858	Destabilizing	0.994	D	0.727	prob.delet.	D	0.585129499	None	None	N
V/N	0.9962	likely_pathogenic	0.9941	pathogenic	-2.081	Highly Destabilizing	0.92	D	0.826	deleterious	None	None	None	None	N
V/P	0.9981	likely_pathogenic	0.9968	pathogenic	-1.278	Destabilizing	0.959	D	0.803	deleterious	None	None	None	None	N
V/Q	0.9964	likely_pathogenic	0.9949	pathogenic	-1.95	Destabilizing	0.965	D	0.803	deleterious	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9947	pathogenic	-1.586	Destabilizing	0.994	D	0.827	deleterious	None	None	None	None	N
V/S	0.9885	likely_pathogenic	0.9838	pathogenic	-2.587	Highly Destabilizing	0.978	D	0.796	deleterious	None	None	None	None	N
V/T	0.9605	likely_pathogenic	0.95	pathogenic	-2.29	Highly Destabilizing	0.911	D	0.691	prob.neutral	None	None	None	None	N
V/W	0.9987	likely_pathogenic	0.998	pathogenic	-1.781	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/Y	0.9914	likely_pathogenic	0.9876	pathogenic	-1.499	Destabilizing	0.999	D	0.775	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.