TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16344	49255;49256;49257	chr2:178614484;178614483;178614482	chr2:179479211;179479210;179479209
N2AB	14703	44332;44333;44334	chr2:178614484;178614483;178614482	chr2:179479211;179479210;179479209
N2A	13776	41551;41552;41553	chr2:178614484;178614483;178614482	chr2:179479211;179479210;179479209
N2B	7279	22060;22061;22062	chr2:178614484;178614483;178614482	chr2:179479211;179479210;179479209
Novex-1	7404	22435;22436;22437	chr2:178614484;178614483;178614482	chr2:179479211;179479210;179479209
Novex-2	7471	22636;22637;22638	chr2:178614484;178614483;178614482	chr2:179479211;179479210;179479209
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-110
• Domain position: 83
• Structural Position: 172
• Q(SASA): 0.0711
• 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/A	None	None	0.014	N	0.326	0.141	0.367229591828	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
V/A	0.6676	likely_pathogenic	0.687	pathogenic	-1.751	Destabilizing	0.014	N	0.326	neutral	N	0.489730102	None	None	N
V/C	0.9047	likely_pathogenic	0.9082	pathogenic	-1.487	Destabilizing	0.994	D	0.803	deleterious	None	None	None	None	N
V/D	0.9987	likely_pathogenic	0.9985	pathogenic	-1.771	Destabilizing	0.978	D	0.864	deleterious	None	None	None	None	N
V/E	0.995	likely_pathogenic	0.995	pathogenic	-1.582	Destabilizing	0.942	D	0.802	deleterious	D	0.674863739	None	None	N
V/F	0.8287	likely_pathogenic	0.861	pathogenic	-0.964	Destabilizing	0.978	D	0.813	deleterious	None	None	None	None	N
V/G	0.9132	likely_pathogenic	0.9199	pathogenic	-2.272	Highly Destabilizing	0.89	D	0.805	deleterious	N	0.515382783	None	None	N
V/H	0.998	likely_pathogenic	0.9982	pathogenic	-1.888	Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
V/I	0.1187	likely_benign	0.1329	benign	-0.332	Destabilizing	0.717	D	0.601	neutral	None	None	None	None	N
V/K	0.9958	likely_pathogenic	0.9958	pathogenic	-1.509	Destabilizing	0.956	D	0.809	deleterious	None	None	None	None	N
V/L	0.6497	likely_pathogenic	0.7051	pathogenic	-0.332	Destabilizing	0.489	N	0.565	neutral	N	0.508384079	None	None	N
V/M	0.6759	likely_pathogenic	0.733	pathogenic	-0.471	Destabilizing	0.99	D	0.733	prob.delet.	D	0.593857357	None	None	N
V/N	0.9939	likely_pathogenic	0.9932	pathogenic	-1.722	Destabilizing	0.978	D	0.879	deleterious	None	None	None	None	N
V/P	0.9966	likely_pathogenic	0.9967	pathogenic	-0.774	Destabilizing	0.978	D	0.845	deleterious	None	None	None	None	N
V/Q	0.9922	likely_pathogenic	0.9923	pathogenic	-1.582	Destabilizing	0.978	D	0.859	deleterious	None	None	None	None	N
V/R	0.9915	likely_pathogenic	0.9909	pathogenic	-1.349	Destabilizing	0.956	D	0.872	deleterious	None	None	None	None	N
V/S	0.9504	likely_pathogenic	0.9496	pathogenic	-2.414	Highly Destabilizing	0.915	D	0.789	deleterious	None	None	None	None	N
V/T	0.7565	likely_pathogenic	0.7669	pathogenic	-2.065	Highly Destabilizing	0.86	D	0.615	neutral	None	None	None	None	N
V/W	0.998	likely_pathogenic	0.9984	pathogenic	-1.353	Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
V/Y	0.9912	likely_pathogenic	0.9918	pathogenic	-0.966	Destabilizing	0.993	D	0.823	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.