TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24653	74182;74183;74184	chr2:178572175;178572174;178572173	chr2:179436902;179436901;179436900
N2AB	23012	69259;69260;69261	chr2:178572175;178572174;178572173	chr2:179436902;179436901;179436900
N2A	22085	66478;66479;66480	chr2:178572175;178572174;178572173	chr2:179436902;179436901;179436900
N2B	15588	46987;46988;46989	chr2:178572175;178572174;178572173	chr2:179436902;179436901;179436900
Novex-1	15713	47362;47363;47364	chr2:178572175;178572174;178572173	chr2:179436902;179436901;179436900
Novex-2	15780	47563;47564;47565	chr2:178572175;178572174;178572173	chr2:179436902;179436901;179436900
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: Fn3-67
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1074
• 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/G	None	None	1.0	D	0.871	0.688	0.910307487806	gnomAD-4.0.0	1.36872E-06	None	None	None	None	N	None	0	0	None	3.8279E-05	0	None	0	0	8.99582E-07	0	0
V/M	None	None	1.0	D	0.744	0.483	0.78595867793	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.879	likely_pathogenic	0.8459	pathogenic	-2.26	Highly Destabilizing	1.0	D	0.626	neutral	D	0.524525094	None	None	N
V/C	0.9813	likely_pathogenic	0.9796	pathogenic	-2.011	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9993	pathogenic	-3.031	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/E	0.9979	likely_pathogenic	0.9969	pathogenic	-2.753	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.557214885	None	None	N
V/F	0.9536	likely_pathogenic	0.9316	pathogenic	-1.235	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/G	0.9812	likely_pathogenic	0.9731	pathogenic	-2.862	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.557214885	None	None	N
V/H	0.9995	likely_pathogenic	0.9992	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/I	0.0936	likely_benign	0.0883	benign	-0.544	Destabilizing	0.878	D	0.304	neutral	None	None	None	None	N
V/K	0.9983	likely_pathogenic	0.9974	pathogenic	-1.869	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/L	0.6331	likely_pathogenic	0.5897	pathogenic	-0.544	Destabilizing	0.97	D	0.567	neutral	D	0.530611098	None	None	N
V/M	0.7831	likely_pathogenic	0.7205	pathogenic	-0.843	Destabilizing	1.0	D	0.744	deleterious	D	0.5453516	None	None	N
V/N	0.9987	likely_pathogenic	0.9979	pathogenic	-2.377	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/P	0.9973	likely_pathogenic	0.9963	pathogenic	-1.092	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Q	0.9975	likely_pathogenic	0.9963	pathogenic	-2.105	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/R	0.9961	likely_pathogenic	0.9947	pathogenic	-1.846	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/S	0.9876	likely_pathogenic	0.9808	pathogenic	-3.006	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.8839	likely_pathogenic	0.8397	pathogenic	-2.567	Highly Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9988	pathogenic	-1.791	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9978	likely_pathogenic	0.9964	pathogenic	-1.434	Destabilizing	1.0	D	0.828	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.