TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14555	43888;43889;43890	chr2:178632231;178632230;178632229	chr2:179496958;179496957;179496956
N2AB	12914	38965;38966;38967	chr2:178632231;178632230;178632229	chr2:179496958;179496957;179496956
N2A	11987	36184;36185;36186	chr2:178632231;178632230;178632229	chr2:179496958;179496957;179496956
N2B	5490	16693;16694;16695	chr2:178632231;178632230;178632229	chr2:179496958;179496957;179496956
Novex-1	5615	17068;17069;17070	chr2:178632231;178632230;178632229	chr2:179496958;179496957;179496956
Novex-2	5682	17269;17270;17271	chr2:178632231;178632230;178632229	chr2:179496958;179496957;179496956
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-96
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.1543
• 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
F/L	rs1452980014	-0.643	0.002	N	0.309	0.215	0.459463830659	gnomAD-2.1.1	4.2E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.72771E-04

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
F/A	0.9526	likely_pathogenic	0.9235	pathogenic	-2.444	Highly Destabilizing	0.617	D	0.743	deleterious	None	None	None	None	N
F/C	0.7227	likely_pathogenic	0.6164	pathogenic	-2.008	Highly Destabilizing	0.99	D	0.831	deleterious	N	0.507700699	None	None	N
F/D	0.995	likely_pathogenic	0.9933	pathogenic	-3.073	Highly Destabilizing	0.972	D	0.861	deleterious	None	None	None	None	N
F/E	0.9897	likely_pathogenic	0.9853	pathogenic	-2.819	Highly Destabilizing	0.92	D	0.86	deleterious	None	None	None	None	N
F/G	0.986	likely_pathogenic	0.978	pathogenic	-2.937	Highly Destabilizing	0.92	D	0.833	deleterious	None	None	None	None	N
F/H	0.9458	likely_pathogenic	0.9264	pathogenic	-1.988	Destabilizing	0.992	D	0.773	deleterious	None	None	None	None	N
F/I	0.3019	likely_benign	0.2187	benign	-0.832	Destabilizing	0.002	N	0.346	neutral	N	0.350672793	None	None	N
F/K	0.9841	likely_pathogenic	0.9779	pathogenic	-2.257	Highly Destabilizing	0.92	D	0.854	deleterious	None	None	None	None	N
F/L	0.8584	likely_pathogenic	0.7528	pathogenic	-0.832	Destabilizing	0.002	N	0.309	neutral	N	0.471083069	None	None	N
F/M	0.661	likely_pathogenic	0.5337	ambiguous	-0.8	Destabilizing	0.85	D	0.695	prob.neutral	None	None	None	None	N
F/N	0.9821	likely_pathogenic	0.9747	pathogenic	-2.906	Highly Destabilizing	0.972	D	0.859	deleterious	None	None	None	None	N
F/P	0.9988	likely_pathogenic	0.9983	pathogenic	-1.383	Destabilizing	0.972	D	0.853	deleterious	None	None	None	None	N
F/Q	0.9781	likely_pathogenic	0.9684	pathogenic	-2.658	Highly Destabilizing	0.972	D	0.86	deleterious	None	None	None	None	N
F/R	0.9656	likely_pathogenic	0.9538	pathogenic	-2.124	Highly Destabilizing	0.92	D	0.856	deleterious	None	None	None	None	N
F/S	0.9542	likely_pathogenic	0.9284	pathogenic	-3.496	Highly Destabilizing	0.896	D	0.833	deleterious	N	0.506839445	None	None	N
F/T	0.9512	likely_pathogenic	0.9313	pathogenic	-3.105	Highly Destabilizing	0.617	D	0.818	deleterious	None	None	None	None	N
F/V	0.4022	ambiguous	0.3021	benign	-1.383	Destabilizing	0.201	N	0.618	neutral	N	0.49008974	None	None	N
F/W	0.717	likely_pathogenic	0.622	pathogenic	-0.285	Destabilizing	0.992	D	0.671	neutral	None	None	None	None	N
F/Y	0.4349	ambiguous	0.3423	ambiguous	-0.674	Destabilizing	0.712	D	0.637	neutral	N	0.511449873	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.