TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28431	85516;85517;85518	chr2:178560841;178560840;178560839	chr2:179425568;179425567;179425566
N2AB	26790	80593;80594;80595	chr2:178560841;178560840;178560839	chr2:179425568;179425567;179425566
N2A	25863	77812;77813;77814	chr2:178560841;178560840;178560839	chr2:179425568;179425567;179425566
N2B	19366	58321;58322;58323	chr2:178560841;178560840;178560839	chr2:179425568;179425567;179425566
Novex-1	19491	58696;58697;58698	chr2:178560841;178560840;178560839	chr2:179425568;179425567;179425566
Novex-2	19558	58897;58898;58899	chr2:178560841;178560840;178560839	chr2:179425568;179425567;179425566
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-143
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2278
• 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
T/I	rs780326294	-0.142	1.0	N	0.849	0.455	0.586235444834	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	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
T/A	0.1749	likely_benign	0.1655	benign	-1.152	Destabilizing	0.999	D	0.652	neutral	N	0.48721372	None	None	N
T/C	0.4589	ambiguous	0.4597	ambiguous	-0.833	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
T/D	0.6871	likely_pathogenic	0.6476	pathogenic	-0.837	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/E	0.4728	ambiguous	0.4452	ambiguous	-0.72	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
T/F	0.2686	likely_benign	0.2506	benign	-0.956	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
T/G	0.5171	ambiguous	0.4823	ambiguous	-1.508	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
T/H	0.2652	likely_benign	0.2455	benign	-1.693	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
T/I	0.1754	likely_benign	0.1719	benign	-0.253	Destabilizing	1.0	D	0.849	deleterious	N	0.496522741	None	None	N
T/K	0.3137	likely_benign	0.304	benign	-0.642	Destabilizing	1.0	D	0.847	deleterious	N	0.473355093	None	None	N
T/L	0.1073	likely_benign	0.1078	benign	-0.253	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
T/M	0.0979	likely_benign	0.1024	benign	-0.128	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
T/N	0.199	likely_benign	0.1795	benign	-0.973	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/P	0.782	likely_pathogenic	0.7698	pathogenic	-0.52	Destabilizing	1.0	D	0.847	deleterious	D	0.524778583	None	None	N
T/Q	0.2749	likely_benign	0.2642	benign	-0.953	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
T/R	0.2499	likely_benign	0.2375	benign	-0.671	Destabilizing	1.0	D	0.854	deleterious	N	0.496560026	None	None	N
T/S	0.1748	likely_benign	0.1644	benign	-1.278	Destabilizing	0.999	D	0.637	neutral	N	0.498061536	None	None	N
T/V	0.1591	likely_benign	0.1652	benign	-0.52	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
T/W	0.6209	likely_pathogenic	0.5885	pathogenic	-0.945	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
T/Y	0.2821	likely_benign	0.2622	benign	-0.646	Destabilizing	1.0	D	0.875	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.