TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21080	63463;63464;63465	chr2:178588169;178588168;178588167	chr2:179452896;179452895;179452894
N2AB	19439	58540;58541;58542	chr2:178588169;178588168;178588167	chr2:179452896;179452895;179452894
N2A	18512	55759;55760;55761	chr2:178588169;178588168;178588167	chr2:179452896;179452895;179452894
N2B	12015	36268;36269;36270	chr2:178588169;178588168;178588167	chr2:179452896;179452895;179452894
Novex-1	12140	36643;36644;36645	chr2:178588169;178588168;178588167	chr2:179452896;179452895;179452894
Novex-2	12207	36844;36845;36846	chr2:178588169;178588168;178588167	chr2:179452896;179452895;179452894
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-41
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1663
• 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
S/A	rs769809225	-0.552	0.76	N	0.423	0.216	0.201204373187	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.35E-05	None	0	0	0
S/A	rs769809225	-0.552	0.76	N	0.423	0.216	0.201204373187	gnomAD-4.0.0	1.61541E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44898E-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
S/A	0.2323	likely_benign	0.2508	benign	-0.292	Destabilizing	0.76	D	0.423	neutral	N	0.478772887	None	None	N
S/C	0.236	likely_benign	0.2543	benign	-0.905	Destabilizing	0.999	D	0.721	prob.delet.	N	0.501538405	None	None	N
S/D	0.8781	likely_pathogenic	0.8767	pathogenic	-2.046	Highly Destabilizing	0.953	D	0.559	neutral	None	None	None	None	N
S/E	0.926	likely_pathogenic	0.911	pathogenic	-1.987	Destabilizing	0.953	D	0.565	neutral	None	None	None	None	N
S/F	0.7412	likely_pathogenic	0.7169	pathogenic	-0.827	Destabilizing	0.991	D	0.798	deleterious	N	0.49749948	None	None	N
S/G	0.2628	likely_benign	0.2737	benign	-0.499	Destabilizing	0.953	D	0.448	neutral	None	None	None	None	N
S/H	0.7337	likely_pathogenic	0.6931	pathogenic	-1.08	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
S/I	0.7948	likely_pathogenic	0.7921	pathogenic	0.156	Stabilizing	0.986	D	0.773	deleterious	None	None	None	None	N
S/K	0.9706	likely_pathogenic	0.9652	pathogenic	-0.445	Destabilizing	0.953	D	0.56	neutral	None	None	None	None	N
S/L	0.4623	ambiguous	0.4644	ambiguous	0.156	Stabilizing	0.91	D	0.653	neutral	None	None	None	None	N
S/M	0.5817	likely_pathogenic	0.5469	ambiguous	0.241	Stabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
S/N	0.5374	ambiguous	0.5544	ambiguous	-1.023	Destabilizing	0.953	D	0.569	neutral	None	None	None	None	N
S/P	0.9928	likely_pathogenic	0.9925	pathogenic	0.037	Stabilizing	0.991	D	0.733	prob.delet.	D	0.535518415	None	None	N
S/Q	0.8786	likely_pathogenic	0.8536	pathogenic	-1.214	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
S/R	0.9446	likely_pathogenic	0.9432	pathogenic	-0.367	Destabilizing	0.986	D	0.746	deleterious	None	None	None	None	N
S/T	0.1296	likely_benign	0.1384	benign	-0.659	Destabilizing	0.046	N	0.391	neutral	N	0.514484065	None	None	N
S/V	0.7158	likely_pathogenic	0.7068	pathogenic	0.037	Stabilizing	0.973	D	0.694	prob.neutral	None	None	None	None	N
S/W	0.8363	likely_pathogenic	0.8095	pathogenic	-1.065	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
S/Y	0.6497	likely_pathogenic	0.624	pathogenic	-0.565	Destabilizing	0.997	D	0.792	deleterious	N	0.498295947	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.