TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16346	49261;49262;49263	chr2:178614478;178614477;178614476	chr2:179479205;179479204;179479203
N2AB	14705	44338;44339;44340	chr2:178614478;178614477;178614476	chr2:179479205;179479204;179479203
N2A	13778	41557;41558;41559	chr2:178614478;178614477;178614476	chr2:179479205;179479204;179479203
N2B	7281	22066;22067;22068	chr2:178614478;178614477;178614476	chr2:179479205;179479204;179479203
Novex-1	7406	22441;22442;22443	chr2:178614478;178614477;178614476	chr2:179479205;179479204;179479203
Novex-2	7473	22642;22643;22644	chr2:178614478;178614477;178614476	chr2:179479205;179479204;179479203
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: 85
• Structural Position: 174
• Q(SASA): 0.1302
• 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	0.999	D	0.632	0.469	0.648895715265	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	0.9538	likely_pathogenic	0.9413	pathogenic	-2.078	Highly Destabilizing	0.999	D	0.632	neutral	D	0.701522176	None	None	N
V/C	0.9772	likely_pathogenic	0.9693	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/D	0.9991	likely_pathogenic	0.9989	pathogenic	-2.169	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/E	0.9974	likely_pathogenic	0.9969	pathogenic	-1.967	Destabilizing	1.0	D	0.875	deleterious	D	0.702712751	None	None	N
V/F	0.9364	likely_pathogenic	0.9238	pathogenic	-1.326	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/G	0.9585	likely_pathogenic	0.9552	pathogenic	-2.617	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.702712751	None	None	N
V/H	0.9994	likely_pathogenic	0.9993	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/I	0.1387	likely_benign	0.1237	benign	-0.589	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
V/K	0.998	likely_pathogenic	0.9976	pathogenic	-1.677	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/L	0.7897	likely_pathogenic	0.7693	pathogenic	-0.589	Destabilizing	0.997	D	0.656	neutral	N	0.412178873	None	None	N
V/M	0.8482	likely_pathogenic	0.8028	pathogenic	-0.862	Destabilizing	1.0	D	0.793	deleterious	D	0.640148694	None	None	N
V/N	0.996	likely_pathogenic	0.995	pathogenic	-1.94	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/P	0.9982	likely_pathogenic	0.9981	pathogenic	-1.056	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/Q	0.998	likely_pathogenic	0.9975	pathogenic	-1.804	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/R	0.9973	likely_pathogenic	0.9967	pathogenic	-1.517	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/S	0.9933	likely_pathogenic	0.9911	pathogenic	-2.693	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/T	0.9604	likely_pathogenic	0.9516	pathogenic	-2.327	Highly Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9992	pathogenic	-1.682	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9956	likely_pathogenic	0.9945	pathogenic	-1.33	Destabilizing	1.0	D	0.841	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.