TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5643	17152;17153;17154	chr2:178731948;178731947;178731946	chr2:179596675;179596674;179596673
N2AB	5326	16201;16202;16203	chr2:178731948;178731947;178731946	chr2:179596675;179596674;179596673
N2A	4399	13420;13421;13422	chr2:178731948;178731947;178731946	chr2:179596675;179596674;179596673
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-40
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1359
• 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
F/L	None	None	0.03	N	0.126	0.23	0.0666544352282	gnomAD-4.0.0	6.86816E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.02931E-07	0	0
F/V	None	None	0.828	N	0.519	0.224	0.43046518545	gnomAD-4.0.0	6.86816E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.02931E-07	0	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
F/A	0.8256	likely_pathogenic	0.8162	pathogenic	-2.467	Highly Destabilizing	0.927	D	0.516	neutral	None	None	None	None	I
F/C	0.5369	ambiguous	0.585	pathogenic	-1.44	Destabilizing	0.999	D	0.559	neutral	N	0.513755268	None	None	I
F/D	0.9632	likely_pathogenic	0.9536	pathogenic	-1.984	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	I
F/E	0.9622	likely_pathogenic	0.9511	pathogenic	-1.817	Destabilizing	0.995	D	0.656	neutral	None	None	None	None	I
F/G	0.9156	likely_pathogenic	0.9073	pathogenic	-2.883	Highly Destabilizing	0.984	D	0.608	neutral	None	None	None	None	I
F/H	0.9107	likely_pathogenic	0.907	pathogenic	-1.25	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	I
F/I	0.2678	likely_benign	0.3077	benign	-1.146	Destabilizing	0.921	D	0.412	neutral	N	0.443239177	None	None	I
F/K	0.9733	likely_pathogenic	0.9671	pathogenic	-1.476	Destabilizing	0.984	D	0.649	neutral	None	None	None	None	I
F/L	0.7324	likely_pathogenic	0.7622	pathogenic	-1.146	Destabilizing	0.03	N	0.126	neutral	N	0.34901672	None	None	I
F/M	0.4935	ambiguous	0.5107	ambiguous	-0.892	Destabilizing	0.991	D	0.57	neutral	None	None	None	None	I
F/N	0.8811	likely_pathogenic	0.8777	pathogenic	-1.724	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	I
F/P	0.8808	likely_pathogenic	0.888	pathogenic	-1.59	Destabilizing	0.088	N	0.443	neutral	None	None	None	None	I
F/Q	0.9423	likely_pathogenic	0.9359	pathogenic	-1.724	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
F/R	0.9528	likely_pathogenic	0.9487	pathogenic	-0.985	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
F/S	0.8565	likely_pathogenic	0.8552	pathogenic	-2.504	Highly Destabilizing	0.979	D	0.587	neutral	N	0.446260839	None	None	I
F/T	0.8549	likely_pathogenic	0.8488	pathogenic	-2.23	Highly Destabilizing	0.984	D	0.568	neutral	None	None	None	None	I
F/V	0.3474	ambiguous	0.3809	ambiguous	-1.59	Destabilizing	0.828	D	0.519	neutral	N	0.445740764	None	None	I
F/W	0.7173	likely_pathogenic	0.7145	pathogenic	-0.172	Destabilizing	0.088	N	0.295	neutral	None	None	None	None	I
F/Y	0.3453	ambiguous	0.3584	ambiguous	-0.5	Destabilizing	0.959	D	0.467	neutral	N	0.513408551	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.