TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19459	58600;58601;58602	chr2:178594018;178594017;178594016	chr2:179458745;179458744;179458743
N2AB	17818	53677;53678;53679	chr2:178594018;178594017;178594016	chr2:179458745;179458744;179458743
N2A	16891	50896;50897;50898	chr2:178594018;178594017;178594016	chr2:179458745;179458744;179458743
N2B	10394	31405;31406;31407	chr2:178594018;178594017;178594016	chr2:179458745;179458744;179458743
Novex-1	10519	31780;31781;31782	chr2:178594018;178594017;178594016	chr2:179458745;179458744;179458743
Novex-2	10586	31981;31982;31983	chr2:178594018;178594017;178594016	chr2:179458745;179458744;179458743
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-118
• Domain position: 69
• Structural Position: 156
• Q(SASA): 0.0884
• 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/E	None	None	0.998	N	0.862	0.537	0.776716716212	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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	0.5414	ambiguous	0.5424	ambiguous	-1.351	Destabilizing	0.543	D	0.389	neutral	N	0.464606111	None	None	N
V/C	0.8901	likely_pathogenic	0.9034	pathogenic	-0.578	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.9973	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/E	0.9923	likely_pathogenic	0.993	pathogenic	-1.775	Destabilizing	0.998	D	0.862	deleterious	N	0.489257732	None	None	N
V/F	0.7036	likely_pathogenic	0.7463	pathogenic	-0.755	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/G	0.8437	likely_pathogenic	0.8438	pathogenic	-1.92	Destabilizing	0.997	D	0.846	deleterious	N	0.489004243	None	None	N
V/H	0.9965	likely_pathogenic	0.9969	pathogenic	-1.985	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/I	0.0929	likely_benign	0.1001	benign	0.264	Stabilizing	0.99	D	0.566	neutral	None	None	None	None	N
V/K	0.9939	likely_pathogenic	0.9942	pathogenic	-0.865	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/L	0.3941	ambiguous	0.4213	ambiguous	0.264	Stabilizing	0.973	D	0.666	neutral	N	0.453437528	None	None	N
V/M	0.4738	ambiguous	0.5181	ambiguous	0.179	Stabilizing	0.999	D	0.681	prob.neutral	N	0.511891185	None	None	N
V/N	0.9897	likely_pathogenic	0.9911	pathogenic	-1.399	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/P	0.9896	likely_pathogenic	0.9888	pathogenic	-0.25	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/Q	0.9873	likely_pathogenic	0.9884	pathogenic	-1.077	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/R	0.985	likely_pathogenic	0.9851	pathogenic	-1.127	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
V/S	0.9247	likely_pathogenic	0.9283	pathogenic	-1.928	Destabilizing	0.995	D	0.843	deleterious	None	None	None	None	N
V/T	0.8026	likely_pathogenic	0.8089	pathogenic	-1.484	Destabilizing	0.992	D	0.707	prob.neutral	None	None	None	None	N
V/W	0.9951	likely_pathogenic	0.996	pathogenic	-1.373	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9807	likely_pathogenic	0.9845	pathogenic	-0.849	Destabilizing	1.0	D	0.793	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.