TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33062	99409;99410;99411	chr2:178538645;178538644;178538643	chr2:179403372;179403371;179403370
N2AB	31421	94486;94487;94488	chr2:178538645;178538644;178538643	chr2:179403372;179403371;179403370
N2A	30494	91705;91706;91707	chr2:178538645;178538644;178538643	chr2:179403372;179403371;179403370
N2B	23997	72214;72215;72216	chr2:178538645;178538644;178538643	chr2:179403372;179403371;179403370
Novex-1	24122	72589;72590;72591	chr2:178538645;178538644;178538643	chr2:179403372;179403371;179403370
Novex-2	24189	72790;72791;72792	chr2:178538645;178538644;178538643	chr2:179403372;179403371;179403370
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-129
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.4712
• 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
G/A	None	None	1.0	N	0.703	0.395	0.306053231325	gnomAD-4.0.0	9.60271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.05002E-05	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
G/A	0.1842	likely_benign	0.2111	benign	-0.258	Destabilizing	1.0	D	0.703	prob.neutral	N	0.498990283	None	None	N
G/C	0.3025	likely_benign	0.3523	ambiguous	-0.912	Destabilizing	1.0	D	0.753	deleterious	N	0.520830747	None	None	N
G/D	0.4071	ambiguous	0.4455	ambiguous	-0.219	Destabilizing	1.0	D	0.761	deleterious	N	0.479368627	None	None	N
G/E	0.4524	ambiguous	0.5133	ambiguous	-0.347	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
G/F	0.7263	likely_pathogenic	0.7858	pathogenic	-0.852	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
G/H	0.5562	ambiguous	0.6203	pathogenic	-0.442	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
G/I	0.5276	ambiguous	0.6015	pathogenic	-0.289	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/K	0.6603	likely_pathogenic	0.7135	pathogenic	-0.698	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
G/L	0.6026	likely_pathogenic	0.6669	pathogenic	-0.289	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/M	0.5979	likely_pathogenic	0.6573	pathogenic	-0.518	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
G/N	0.2938	likely_benign	0.3244	benign	-0.406	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/P	0.8915	likely_pathogenic	0.9128	pathogenic	-0.245	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/Q	0.4778	ambiguous	0.539	ambiguous	-0.598	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
G/R	0.5463	ambiguous	0.6071	pathogenic	-0.347	Destabilizing	1.0	D	0.795	deleterious	N	0.486735378	None	None	N
G/S	0.1164	likely_benign	0.1266	benign	-0.633	Destabilizing	1.0	D	0.771	deleterious	D	0.527856007	None	None	N
G/T	0.2572	likely_benign	0.2874	benign	-0.668	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/V	0.3878	ambiguous	0.4555	ambiguous	-0.245	Destabilizing	1.0	D	0.782	deleterious	D	0.531844658	None	None	N
G/W	0.6773	likely_pathogenic	0.7497	pathogenic	-1.031	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
G/Y	0.6027	likely_pathogenic	0.6822	pathogenic	-0.661	Destabilizing	1.0	D	0.769	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.