TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6506	19741;19742;19743	chr2:178728308;178728307;178728306	chr2:179593035;179593034;179593033
N2AB	6189	18790;18791;18792	chr2:178728308;178728307;178728306	chr2:179593035;179593034;179593033
N2A	5262	16009;16010;16011	chr2:178728308;178728307;178728306	chr2:179593035;179593034;179593033
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-49
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4412
• 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/D	rs1401335381	-0.042	1.0	D	0.814	0.783	0.594932130068	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
G/D	rs1401335381	-0.042	1.0	D	0.814	0.783	0.594932130068	gnomAD-4.0.0	2.05353E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69905E-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	0.7746	likely_pathogenic	0.6636	pathogenic	-0.212	Destabilizing	1.0	D	0.782	deleterious	D	0.576001844	None	None	I
G/C	0.9715	likely_pathogenic	0.936	pathogenic	-0.878	Destabilizing	1.0	D	0.697	prob.neutral	D	0.63861486	None	None	I
G/D	0.9885	likely_pathogenic	0.9742	pathogenic	-0.171	Destabilizing	1.0	D	0.814	deleterious	D	0.577969884	None	None	I
G/E	0.9916	likely_pathogenic	0.9774	pathogenic	-0.304	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/F	0.995	likely_pathogenic	0.9878	pathogenic	-0.796	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
G/H	0.9966	likely_pathogenic	0.9917	pathogenic	-0.549	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
G/I	0.9873	likely_pathogenic	0.9667	pathogenic	-0.205	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
G/K	0.9955	likely_pathogenic	0.9898	pathogenic	-0.729	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/L	0.9914	likely_pathogenic	0.9813	pathogenic	-0.205	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
G/M	0.9963	likely_pathogenic	0.9902	pathogenic	-0.384	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
G/N	0.9925	likely_pathogenic	0.983	pathogenic	-0.379	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
G/P	0.997	likely_pathogenic	0.994	pathogenic	-0.171	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
G/Q	0.9934	likely_pathogenic	0.9847	pathogenic	-0.589	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/R	0.9816	likely_pathogenic	0.9612	pathogenic	-0.409	Destabilizing	1.0	D	0.797	deleterious	D	0.598511096	None	None	I
G/S	0.8105	likely_pathogenic	0.669	pathogenic	-0.618	Destabilizing	1.0	D	0.829	deleterious	D	0.573992724	None	None	I
G/T	0.9687	likely_pathogenic	0.9263	pathogenic	-0.66	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/V	0.9696	likely_pathogenic	0.9243	pathogenic	-0.171	Destabilizing	1.0	D	0.757	deleterious	D	0.654230613	None	None	I
G/W	0.9909	likely_pathogenic	0.9756	pathogenic	-1.001	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
G/Y	0.9949	likely_pathogenic	0.9854	pathogenic	-0.611	Destabilizing	1.0	D	0.736	prob.delet.	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.