TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17395	52408;52409;52410	chr2:178608828;178608827;178608826	chr2:179473555;179473554;179473553
N2AB	15754	47485;47486;47487	chr2:178608828;178608827;178608826	chr2:179473555;179473554;179473553
N2A	14827	44704;44705;44706	chr2:178608828;178608827;178608826	chr2:179473555;179473554;179473553
N2B	8330	25213;25214;25215	chr2:178608828;178608827;178608826	chr2:179473555;179473554;179473553
Novex-1	8455	25588;25589;25590	chr2:178608828;178608827;178608826	chr2:179473555;179473554;179473553
Novex-2	8522	25789;25790;25791	chr2:178608828;178608827;178608826	chr2:179473555;179473554;179473553
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: Fn3-14
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4383
• 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
D/E	rs1479797110	None	1.0	N	0.402	0.214	0.342400092842	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
D/E	rs1479797110	None	1.0	N	0.402	0.214	0.342400092842	gnomAD-4.0.0	4.10842E-06	None	None	None	None	I	None	8.98257E-05	0	None	0	0	None	0	0	0	0	4.97463E-05

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	0.8705	likely_pathogenic	0.8915	pathogenic	-0.293	Destabilizing	1.0	D	0.737	prob.delet.	N	0.486306261	None	None	I
D/C	0.9729	likely_pathogenic	0.9752	pathogenic	0.123	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/E	0.6968	likely_pathogenic	0.7422	pathogenic	-0.311	Destabilizing	1.0	D	0.402	neutral	N	0.478722164	None	None	I
D/F	0.9588	likely_pathogenic	0.968	pathogenic	-0.327	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
D/G	0.8985	likely_pathogenic	0.9133	pathogenic	-0.483	Destabilizing	1.0	D	0.703	prob.neutral	N	0.497017457	None	None	I
D/H	0.9084	likely_pathogenic	0.9255	pathogenic	-0.27	Destabilizing	1.0	D	0.644	neutral	N	0.482369468	None	None	I
D/I	0.9299	likely_pathogenic	0.9536	pathogenic	0.159	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
D/K	0.9609	likely_pathogenic	0.9699	pathogenic	0.3	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
D/L	0.9055	likely_pathogenic	0.9312	pathogenic	0.159	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
D/M	0.9742	likely_pathogenic	0.9795	pathogenic	0.379	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
D/N	0.5618	ambiguous	0.5973	pathogenic	0.058	Stabilizing	1.0	D	0.668	neutral	N	0.470973483	None	None	I
D/P	0.9952	likely_pathogenic	0.9964	pathogenic	0.03	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
D/Q	0.9209	likely_pathogenic	0.9343	pathogenic	0.089	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
D/R	0.9525	likely_pathogenic	0.9588	pathogenic	0.387	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
D/S	0.7807	likely_pathogenic	0.7965	pathogenic	-0.046	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/T	0.9033	likely_pathogenic	0.9265	pathogenic	0.101	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
D/V	0.8472	likely_pathogenic	0.8838	pathogenic	0.03	Stabilizing	1.0	D	0.768	deleterious	N	0.4942063	None	None	I
D/W	0.9895	likely_pathogenic	0.9911	pathogenic	-0.226	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
D/Y	0.8136	likely_pathogenic	0.8556	pathogenic	-0.101	Destabilizing	1.0	D	0.681	prob.neutral	N	0.512342263	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.