TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18833	56722;56723;56724	chr2:178599296;178599295;178599294	chr2:179464023;179464022;179464021
N2AB	17192	51799;51800;51801	chr2:178599296;178599295;178599294	chr2:179464023;179464022;179464021
N2A	16265	49018;49019;49020	chr2:178599296;178599295;178599294	chr2:179464023;179464022;179464021
N2B	9768	29527;29528;29529	chr2:178599296;178599295;178599294	chr2:179464023;179464022;179464021
Novex-1	9893	29902;29903;29904	chr2:178599296;178599295;178599294	chr2:179464023;179464022;179464021
Novex-2	9960	30103;30104;30105	chr2:178599296;178599295;178599294	chr2:179464023;179464022;179464021
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-24
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.4795
• 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	rs1553665072	None	0.863	N	0.501	0.186	0.566593488784	gnomAD-4.0.0	1.6052E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46054E-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	0.2496	likely_benign	0.2283	benign	-1.061	Destabilizing	0.046	N	0.235	neutral	N	0.497066167	None	None	N
V/C	0.6947	likely_pathogenic	0.6568	pathogenic	-0.773	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
V/D	0.6152	likely_pathogenic	0.5036	ambiguous	-0.864	Destabilizing	0.991	D	0.725	prob.delet.	N	0.496682164	None	None	N
V/E	0.4969	ambiguous	0.3867	ambiguous	-0.903	Destabilizing	0.986	D	0.701	prob.neutral	None	None	None	None	N
V/F	0.2226	likely_benign	0.1928	benign	-0.852	Destabilizing	0.997	D	0.671	neutral	N	0.495951446	None	None	N
V/G	0.2563	likely_benign	0.2447	benign	-1.307	Destabilizing	0.964	D	0.672	neutral	N	0.518385588	None	None	N
V/H	0.6487	likely_pathogenic	0.5667	pathogenic	-0.732	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
V/I	0.0841	likely_benign	0.0834	benign	-0.513	Destabilizing	0.863	D	0.501	neutral	N	0.461588156	None	None	N
V/K	0.5973	likely_pathogenic	0.4672	ambiguous	-1.005	Destabilizing	0.986	D	0.701	prob.neutral	None	None	None	None	N
V/L	0.2413	likely_benign	0.2067	benign	-0.513	Destabilizing	0.863	D	0.513	neutral	N	0.491044271	None	None	N
V/M	0.1717	likely_benign	0.154	benign	-0.47	Destabilizing	0.998	D	0.64	neutral	None	None	None	None	N
V/N	0.3023	likely_benign	0.259	benign	-0.808	Destabilizing	0.993	D	0.728	prob.delet.	None	None	None	None	N
V/P	0.9192	likely_pathogenic	0.9062	pathogenic	-0.66	Destabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	N
V/Q	0.4044	ambiguous	0.3395	benign	-1.002	Destabilizing	0.993	D	0.691	prob.neutral	None	None	None	None	N
V/R	0.5479	ambiguous	0.4317	ambiguous	-0.416	Destabilizing	0.993	D	0.73	prob.delet.	None	None	None	None	N
V/S	0.2418	likely_benign	0.2278	benign	-1.241	Destabilizing	0.973	D	0.634	neutral	None	None	None	None	N
V/T	0.2337	likely_benign	0.2195	benign	-1.178	Destabilizing	0.953	D	0.545	neutral	None	None	None	None	N
V/W	0.8547	likely_pathogenic	0.7996	pathogenic	-0.996	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
V/Y	0.588	likely_pathogenic	0.5146	ambiguous	-0.718	Destabilizing	0.998	D	0.677	prob.neutral	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.