TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25171	75736;75737;75738	chr2:178570621;178570620;178570619	chr2:179435348;179435347;179435346
N2AB	23530	70813;70814;70815	chr2:178570621;178570620;178570619	chr2:179435348;179435347;179435346
N2A	22603	68032;68033;68034	chr2:178570621;178570620;178570619	chr2:179435348;179435347;179435346
N2B	16106	48541;48542;48543	chr2:178570621;178570620;178570619	chr2:179435348;179435347;179435346
Novex-1	16231	48916;48917;48918	chr2:178570621;178570620;178570619	chr2:179435348;179435347;179435346
Novex-2	16298	49117;49118;49119	chr2:178570621;178570620;178570619	chr2:179435348;179435347;179435346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-134
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.1062
• 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/I	None	None	0.025	N	0.332	0.061	0.162503812791	gnomAD-4.0.0	1.59191E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85925E-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	0.5354	ambiguous	0.5508	ambiguous	-1.857	Destabilizing	0.773	D	0.669	neutral	D	0.534755763	None	None	N
V/C	0.7648	likely_pathogenic	0.7829	pathogenic	-1.63	Destabilizing	0.154	N	0.585	neutral	None	None	None	None	N
V/D	0.9295	likely_pathogenic	0.9439	pathogenic	-2.125	Highly Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
V/E	0.8622	likely_pathogenic	0.8944	pathogenic	-1.976	Destabilizing	0.994	D	0.853	deleterious	D	0.535516232	None	None	N
V/F	0.3503	ambiguous	0.3981	ambiguous	-1.209	Destabilizing	0.975	D	0.767	deleterious	None	None	None	None	N
V/G	0.6482	likely_pathogenic	0.6835	pathogenic	-2.338	Highly Destabilizing	0.983	D	0.871	deleterious	N	0.512803621	None	None	N
V/H	0.896	likely_pathogenic	0.9182	pathogenic	-2.047	Highly Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
V/I	0.0788	likely_benign	0.0787	benign	-0.556	Destabilizing	0.025	N	0.332	neutral	N	0.403035711	None	None	N
V/K	0.8511	likely_pathogenic	0.8956	pathogenic	-1.46	Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	N
V/L	0.2849	likely_benign	0.3168	benign	-0.556	Destabilizing	0.369	N	0.6	neutral	N	0.51778066	None	None	N
V/M	0.25	likely_benign	0.2785	benign	-0.656	Destabilizing	0.975	D	0.694	prob.neutral	None	None	None	None	N
V/N	0.7589	likely_pathogenic	0.7641	pathogenic	-1.601	Destabilizing	0.996	D	0.88	deleterious	None	None	None	None	N
V/P	0.9732	likely_pathogenic	0.9809	pathogenic	-0.959	Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	N
V/Q	0.8029	likely_pathogenic	0.8437	pathogenic	-1.553	Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
V/R	0.8043	likely_pathogenic	0.8583	pathogenic	-1.231	Destabilizing	0.996	D	0.882	deleterious	None	None	None	None	N
V/S	0.6444	likely_pathogenic	0.6692	pathogenic	-2.26	Highly Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
V/T	0.612	likely_pathogenic	0.6365	pathogenic	-1.971	Destabilizing	0.916	D	0.703	prob.neutral	None	None	None	None	N
V/W	0.9413	likely_pathogenic	0.9585	pathogenic	-1.616	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
V/Y	0.8038	likely_pathogenic	0.8489	pathogenic	-1.246	Destabilizing	0.987	D	0.753	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.