TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9476	28651;28652;28653	chr2:178710671;178710670;178710669	chr2:179575398;179575397;179575396
N2AB	9159	27700;27701;27702	chr2:178710671;178710670;178710669	chr2:179575398;179575397;179575396
N2A	8232	24919;24920;24921	chr2:178710671;178710670;178710669	chr2:179575398;179575397;179575396
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-80
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.1947
• 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/V	None	None	1.0	None	0.827	0.599	0.951045865265	gnomAD-4.0.0	1.59372E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85922E-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	0.6527	likely_pathogenic	0.8248	pathogenic	-0.399	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
G/C	0.9011	likely_pathogenic	0.959	pathogenic	-0.937	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/D	0.8671	likely_pathogenic	0.9462	pathogenic	-0.985	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/E	0.8866	likely_pathogenic	0.9577	pathogenic	-1.148	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/F	0.9814	likely_pathogenic	0.9921	pathogenic	-1.097	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/H	0.9663	likely_pathogenic	0.9913	pathogenic	-0.652	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/I	0.9759	likely_pathogenic	0.9921	pathogenic	-0.533	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/K	0.9596	likely_pathogenic	0.989	pathogenic	-1.103	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/L	0.9632	likely_pathogenic	0.9877	pathogenic	-0.533	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/M	0.9763	likely_pathogenic	0.992	pathogenic	-0.564	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/N	0.9229	likely_pathogenic	0.9726	pathogenic	-0.711	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/P	0.9975	likely_pathogenic	0.9991	pathogenic	-0.456	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/Q	0.9107	likely_pathogenic	0.9736	pathogenic	-1.026	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/R	0.8926	likely_pathogenic	0.9638	pathogenic	-0.569	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/S	0.5158	ambiguous	0.7287	pathogenic	-0.795	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/T	0.8825	likely_pathogenic	0.9594	pathogenic	-0.901	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
G/V	0.9483	likely_pathogenic	0.9805	pathogenic	-0.456	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/W	0.948	likely_pathogenic	0.979	pathogenic	-1.253	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/Y	0.9661	likely_pathogenic	0.9888	pathogenic	-0.932	Destabilizing	1.0	D	0.829	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.