TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27615	83068;83069;83070	chr2:178563289;178563288;178563287	chr2:179428016;179428015;179428014
N2AB	25974	78145;78146;78147	chr2:178563289;178563288;178563287	chr2:179428016;179428015;179428014
N2A	25047	75364;75365;75366	chr2:178563289;178563288;178563287	chr2:179428016;179428015;179428014
N2B	18550	55873;55874;55875	chr2:178563289;178563288;178563287	chr2:179428016;179428015;179428014
Novex-1	18675	56248;56249;56250	chr2:178563289;178563288;178563287	chr2:179428016;179428015;179428014
Novex-2	18742	56449;56450;56451	chr2:178563289;178563288;178563287	chr2:179428016;179428015;179428014
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-89
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.126
• 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
D/H	None	None	0.984	N	0.613	0.426	0.330589388543	gnomAD-4.0.0	3.18313E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86558E-05	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
D/A	0.1232	likely_benign	0.1105	benign	0.082	Stabilizing	0.822	D	0.507	neutral	N	0.469975566	None	None	N
D/C	0.5302	ambiguous	0.4783	ambiguous	-0.063	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
D/E	0.0859	likely_benign	0.0906	benign	-0.246	Destabilizing	0.058	N	0.429	neutral	N	0.421488186	None	None	N
D/F	0.541	ambiguous	0.4876	ambiguous	-0.065	Destabilizing	0.998	D	0.638	neutral	None	None	None	None	N
D/G	0.1213	likely_benign	0.1027	benign	-0.021	Destabilizing	0.698	D	0.624	neutral	N	0.440727307	None	None	N
D/H	0.2855	likely_benign	0.2338	benign	0.522	Stabilizing	0.984	D	0.613	neutral	N	0.469469454	None	None	N
D/I	0.2903	likely_benign	0.2476	benign	0.28	Stabilizing	0.978	D	0.651	neutral	None	None	None	None	N
D/K	0.2482	likely_benign	0.2075	benign	0.461	Stabilizing	0.754	D	0.575	neutral	None	None	None	None	N
D/L	0.2921	likely_benign	0.2472	benign	0.28	Stabilizing	0.956	D	0.636	neutral	None	None	None	None	N
D/M	0.42	ambiguous	0.3918	ambiguous	0.085	Stabilizing	0.998	D	0.644	neutral	None	None	None	None	N
D/N	0.0981	likely_benign	0.0883	benign	0.322	Stabilizing	0.032	N	0.477	neutral	N	0.480805848	None	None	N
D/P	0.4402	ambiguous	0.3935	ambiguous	0.233	Stabilizing	0.978	D	0.609	neutral	None	None	None	None	N
D/Q	0.2396	likely_benign	0.2042	benign	0.307	Stabilizing	0.956	D	0.648	neutral	None	None	None	None	N
D/R	0.3273	likely_benign	0.2659	benign	0.665	Stabilizing	0.956	D	0.614	neutral	None	None	None	None	N
D/S	0.0997	likely_benign	0.0899	benign	0.199	Stabilizing	0.754	D	0.618	neutral	None	None	None	None	N
D/T	0.1551	likely_benign	0.1401	benign	0.281	Stabilizing	0.956	D	0.581	neutral	None	None	None	None	N
D/V	0.1628	likely_benign	0.1399	benign	0.233	Stabilizing	0.971	D	0.636	neutral	N	0.504992216	None	None	N
D/W	0.8017	likely_pathogenic	0.7425	pathogenic	-0.05	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
D/Y	0.2665	likely_benign	0.2242	benign	0.159	Stabilizing	0.997	D	0.638	neutral	N	0.467152049	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.