TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16064	48415;48416;48417	chr2:178616601;178616600;178616599	chr2:179481328;179481327;179481326
N2AB	14423	43492;43493;43494	chr2:178616601;178616600;178616599	chr2:179481328;179481327;179481326
N2A	13496	40711;40712;40713	chr2:178616601;178616600;178616599	chr2:179481328;179481327;179481326
N2B	6999	21220;21221;21222	chr2:178616601;178616600;178616599	chr2:179481328;179481327;179481326
Novex-1	7124	21595;21596;21597	chr2:178616601;178616600;178616599	chr2:179481328;179481327;179481326
Novex-2	7191	21796;21797;21798	chr2:178616601;178616600;178616599	chr2:179481328;179481327;179481326
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: Fn3-4
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2626
• 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/C	None	None	None	N	0.435	0.156	0.225215365344	gnomAD-4.0.0	1.59429E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86357E-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	0.1587	likely_benign	0.2104	benign	-2.186	Highly Destabilizing	0.007	N	0.365	neutral	None	None	None	None	N
F/C	0.1453	likely_benign	0.1812	benign	-1.903	Destabilizing	None	N	0.435	neutral	N	0.448060631	None	None	N
F/D	0.7161	likely_pathogenic	0.7739	pathogenic	-1.514	Destabilizing	0.136	N	0.609	neutral	None	None	None	None	N
F/E	0.7334	likely_pathogenic	0.7971	pathogenic	-1.335	Destabilizing	0.136	N	0.585	neutral	None	None	None	None	N
F/G	0.4912	ambiguous	0.5927	pathogenic	-2.572	Highly Destabilizing	0.061	N	0.473	neutral	None	None	None	None	N
F/H	0.4534	ambiguous	0.5444	ambiguous	-1.078	Destabilizing	0.214	N	0.539	neutral	None	None	None	None	N
F/I	0.0921	likely_benign	0.0963	benign	-0.971	Destabilizing	0.005	N	0.35	neutral	N	0.37351238	None	None	N
F/K	0.6654	likely_pathogenic	0.7863	pathogenic	-1.92	Destabilizing	0.072	N	0.578	neutral	None	None	None	None	N
F/L	0.572	likely_pathogenic	0.6619	pathogenic	-0.971	Destabilizing	0.005	N	0.345	neutral	N	0.419086551	None	None	N
F/M	0.2503	likely_benign	0.3283	benign	-1.003	Destabilizing	0.356	N	0.505	neutral	None	None	None	None	N
F/N	0.4745	ambiguous	0.5763	pathogenic	-2.3	Highly Destabilizing	0.356	N	0.651	neutral	None	None	None	None	N
F/P	0.5475	ambiguous	0.6829	pathogenic	-1.379	Destabilizing	None	N	0.458	neutral	None	None	None	None	N
F/Q	0.5933	likely_pathogenic	0.7092	pathogenic	-2.133	Highly Destabilizing	0.356	N	0.657	neutral	None	None	None	None	N
F/R	0.5794	likely_pathogenic	0.6911	pathogenic	-1.591	Destabilizing	0.214	N	0.655	neutral	None	None	None	None	N
F/S	0.1969	likely_benign	0.2425	benign	-3.047	Highly Destabilizing	0.024	N	0.44	neutral	N	0.47398514	None	None	N
F/T	0.1348	likely_benign	0.176	benign	-2.75	Highly Destabilizing	0.031	N	0.412	neutral	None	None	None	None	N
F/V	0.0864	likely_benign	0.0941	benign	-1.379	Destabilizing	None	N	0.25	neutral	N	0.293700836	None	None	N
F/W	0.3584	ambiguous	0.4211	ambiguous	-0.18	Destabilizing	0.356	N	0.528	neutral	None	None	None	None	N
F/Y	0.1397	likely_benign	0.1665	benign	-0.537	Destabilizing	None	N	0.239	neutral	N	0.466446521	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.