TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2613	8062;8063;8064	chr2:178773127;178773126;178773125	chr2:179637854;179637853;179637852
N2AB	2613	8062;8063;8064	chr2:178773127;178773126;178773125	chr2:179637854;179637853;179637852
N2A	2613	8062;8063;8064	chr2:178773127;178773126;178773125	chr2:179637854;179637853;179637852
N2B	2567	7924;7925;7926	chr2:178773127;178773126;178773125	chr2:179637854;179637853;179637852
Novex-1	2567	7924;7925;7926	chr2:178773127;178773126;178773125	chr2:179637854;179637853;179637852
Novex-2	2567	7924;7925;7926	chr2:178773127;178773126;178773125	chr2:179637854;179637853;179637852
Novex-3	2613	8062;8063;8064	chr2:178773127;178773126;178773125	chr2:179637854;179637853;179637852

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-15
• Domain position: 81
• Structural Position: 172
• Q(SASA): 0.1998
• 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/E	None	None	0.993	N	0.705	0.237	0.318252033908	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1281	likely_benign	0.1275	benign	-0.438	Destabilizing	0.053	N	0.297	neutral	N	0.302323849	None	None	N
G/C	0.3875	ambiguous	0.3714	ambiguous	-0.913	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/D	0.9644	likely_pathogenic	0.9592	pathogenic	-0.544	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
G/E	0.9536	likely_pathogenic	0.9434	pathogenic	-0.485	Destabilizing	0.993	D	0.705	prob.neutral	N	0.44397319	None	None	N
G/F	0.9708	likely_pathogenic	0.9594	pathogenic	-0.587	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
G/H	0.9777	likely_pathogenic	0.9709	pathogenic	-1.309	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/I	0.8459	likely_pathogenic	0.8218	pathogenic	0.347	Stabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
G/K	0.9821	likely_pathogenic	0.9771	pathogenic	-0.7	Destabilizing	0.995	D	0.712	prob.delet.	None	None	None	None	N
G/L	0.8882	likely_pathogenic	0.859	pathogenic	0.347	Stabilizing	0.995	D	0.741	deleterious	None	None	None	None	N
G/M	0.9193	likely_pathogenic	0.9009	pathogenic	0.027	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/N	0.9486	likely_pathogenic	0.9436	pathogenic	-0.603	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
G/P	0.9969	likely_pathogenic	0.9957	pathogenic	0.131	Stabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
G/Q	0.9519	likely_pathogenic	0.9394	pathogenic	-0.547	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
G/R	0.9448	likely_pathogenic	0.9297	pathogenic	-0.797	Destabilizing	0.997	D	0.761	deleterious	N	0.443165023	None	None	N
G/S	0.2641	likely_benign	0.2679	benign	-1.071	Destabilizing	0.966	D	0.454	neutral	None	None	None	None	N
G/T	0.5963	likely_pathogenic	0.5944	pathogenic	-0.877	Destabilizing	0.995	D	0.687	prob.neutral	None	None	None	None	N
G/V	0.665	likely_pathogenic	0.6353	pathogenic	0.131	Stabilizing	0.987	D	0.725	prob.delet.	N	0.434016	None	None	N
G/W	0.9702	likely_pathogenic	0.9551	pathogenic	-1.113	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/Y	0.9683	likely_pathogenic	0.9559	pathogenic	-0.547	Destabilizing	1.0	D	0.83	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.