TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21567	64924;64925;64926	chr2:178584942;178584941;178584940	chr2:179449669;179449668;179449667
N2AB	19926	60001;60002;60003	chr2:178584942;178584941;178584940	chr2:179449669;179449668;179449667
N2A	18999	57220;57221;57222	chr2:178584942;178584941;178584940	chr2:179449669;179449668;179449667
N2B	12502	37729;37730;37731	chr2:178584942;178584941;178584940	chr2:179449669;179449668;179449667
Novex-1	12627	38104;38105;38106	chr2:178584942;178584941;178584940	chr2:179449669;179449668;179449667
Novex-2	12694	38305;38306;38307	chr2:178584942;178584941;178584940	chr2:179449669;179449668;179449667
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: Fn3-44
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.3195
• 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/S	None	None	0.959	N	0.6	0.413	0.567244179635	gnomAD-4.0.0	1.59249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86008E-06	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	0.936	likely_pathogenic	0.9424	pathogenic	-3.133	Highly Destabilizing	0.863	D	0.456	neutral	None	None	None	None	N
F/C	0.7161	likely_pathogenic	0.7033	pathogenic	-1.768	Destabilizing	0.999	D	0.61	neutral	N	0.497028881	None	None	N
F/D	0.9953	likely_pathogenic	0.9962	pathogenic	-3.826	Highly Destabilizing	0.997	D	0.657	neutral	None	None	None	None	N
F/E	0.9945	likely_pathogenic	0.9955	pathogenic	-3.611	Highly Destabilizing	0.997	D	0.651	neutral	None	None	None	None	N
F/G	0.9854	likely_pathogenic	0.9866	pathogenic	-3.554	Highly Destabilizing	0.969	D	0.647	neutral	None	None	None	None	N
F/H	0.9823	likely_pathogenic	0.9849	pathogenic	-2.302	Highly Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
F/I	0.3688	ambiguous	0.315	benign	-1.731	Destabilizing	0.134	N	0.257	neutral	N	0.390437347	None	None	N
F/K	0.9952	likely_pathogenic	0.9961	pathogenic	-2.298	Highly Destabilizing	0.991	D	0.653	neutral	None	None	None	None	N
F/L	0.8749	likely_pathogenic	0.817	pathogenic	-1.731	Destabilizing	0.005	N	0.189	neutral	N	0.350523804	None	None	N
F/M	0.6505	likely_pathogenic	0.5898	pathogenic	-1.412	Destabilizing	0.579	D	0.293	neutral	None	None	None	None	N
F/N	0.9872	likely_pathogenic	0.9889	pathogenic	-2.849	Highly Destabilizing	0.997	D	0.654	neutral	None	None	None	None	N
F/P	0.9921	likely_pathogenic	0.9924	pathogenic	-2.214	Highly Destabilizing	0.997	D	0.66	neutral	None	None	None	None	N
F/Q	0.9903	likely_pathogenic	0.9921	pathogenic	-2.777	Highly Destabilizing	0.991	D	0.661	neutral	None	None	None	None	N
F/R	0.9892	likely_pathogenic	0.991	pathogenic	-1.867	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	N
F/S	0.9642	likely_pathogenic	0.9703	pathogenic	-3.32	Highly Destabilizing	0.959	D	0.6	neutral	N	0.423685916	None	None	N
F/T	0.9349	likely_pathogenic	0.94	pathogenic	-3.0	Highly Destabilizing	0.969	D	0.56	neutral	None	None	None	None	N
F/V	0.3977	ambiguous	0.3682	ambiguous	-2.214	Highly Destabilizing	0.509	D	0.406	neutral	N	0.353839041	None	None	N
F/W	0.8145	likely_pathogenic	0.8191	pathogenic	-0.674	Destabilizing	0.999	D	0.489	neutral	None	None	None	None	N
F/Y	0.619	likely_pathogenic	0.6226	pathogenic	-1.126	Destabilizing	0.986	D	0.507	neutral	N	0.444330547	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.