TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23713	71362;71363;71364	chr2:178574995;178574994;178574993	chr2:179439722;179439721;179439720
N2AB	22072	66439;66440;66441	chr2:178574995;178574994;178574993	chr2:179439722;179439721;179439720
N2A	21145	63658;63659;63660	chr2:178574995;178574994;178574993	chr2:179439722;179439721;179439720
N2B	14648	44167;44168;44169	chr2:178574995;178574994;178574993	chr2:179439722;179439721;179439720
Novex-1	14773	44542;44543;44544	chr2:178574995;178574994;178574993	chr2:179439722;179439721;179439720
Novex-2	14840	44743;44744;44745	chr2:178574995;178574994;178574993	chr2:179439722;179439721;179439720
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-130
• Domain position: 77
• Structural Position: 164
• Q(SASA): 0.2832
• Predicted PPI site: I

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/E	None	None	0.997	D	0.806	0.792	0.658074552805	gnomAD-4.0.0	1.59226E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8594E-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
G/A	0.6555	likely_pathogenic	0.63	pathogenic	-0.355	Destabilizing	0.983	D	0.603	neutral	D	0.589924594	None	None	I
G/C	0.8361	likely_pathogenic	0.8092	pathogenic	-0.89	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/D	0.9381	likely_pathogenic	0.9221	pathogenic	-0.861	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	I
G/E	0.9564	likely_pathogenic	0.9464	pathogenic	-1.025	Destabilizing	0.997	D	0.806	deleterious	D	0.552097366	None	None	I
G/F	0.991	likely_pathogenic	0.9878	pathogenic	-1.064	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/H	0.9778	likely_pathogenic	0.9705	pathogenic	-0.644	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/I	0.9893	likely_pathogenic	0.9848	pathogenic	-0.49	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
G/K	0.9687	likely_pathogenic	0.9585	pathogenic	-1.04	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	I
G/L	0.9813	likely_pathogenic	0.9758	pathogenic	-0.49	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	I
G/M	0.983	likely_pathogenic	0.9777	pathogenic	-0.527	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/N	0.9423	likely_pathogenic	0.9325	pathogenic	-0.632	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	I
G/P	0.9987	likely_pathogenic	0.9982	pathogenic	-0.413	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	I
G/Q	0.9432	likely_pathogenic	0.9311	pathogenic	-0.937	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/R	0.9325	likely_pathogenic	0.9132	pathogenic	-0.538	Destabilizing	0.997	D	0.823	deleterious	D	0.627504907	None	None	I
G/S	0.5673	likely_pathogenic	0.5249	ambiguous	-0.726	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	I
G/T	0.8949	likely_pathogenic	0.8621	pathogenic	-0.831	Destabilizing	0.713	D	0.517	neutral	None	None	None	None	I
G/V	0.9697	likely_pathogenic	0.9582	pathogenic	-0.413	Destabilizing	0.995	D	0.787	deleterious	D	0.62811032	None	None	I
G/W	0.9814	likely_pathogenic	0.9759	pathogenic	-1.23	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/Y	0.9821	likely_pathogenic	0.9764	pathogenic	-0.901	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I

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.