TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5234	15925;15926;15927	chr2:178733689;178733688;178733687	chr2:179598416;179598415;179598414
N2AB	4917	14974;14975;14976	chr2:178733689;178733688;178733687	chr2:179598416;179598415;179598414
N2A	3990	12193;12194;12195	chr2:178733689;178733688;178733687	chr2:179598416;179598415;179598414
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-35
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.2369
• 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	None	None	None	N	0.236	0.1	0.0762999501168	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0907	likely_benign	0.0937	benign	-1.854	Destabilizing	0.007	N	0.486	neutral	None	None	None	None	N
F/C	0.081	likely_benign	0.0888	benign	-1.208	Destabilizing	0.56	D	0.699	prob.neutral	N	0.442620588	None	None	N
F/D	0.1421	likely_benign	0.1707	benign	-0.096	Destabilizing	0.072	N	0.637	neutral	None	None	None	None	N
F/E	0.2943	likely_benign	0.3784	ambiguous	-0.013	Destabilizing	0.016	N	0.602	neutral	None	None	None	None	N
F/G	0.2174	likely_benign	0.2645	benign	-2.16	Highly Destabilizing	0.016	N	0.569	neutral	None	None	None	None	N
F/H	0.1273	likely_benign	0.1724	benign	-0.328	Destabilizing	None	N	0.321	neutral	None	None	None	None	N
F/I	0.0743	likely_benign	0.0917	benign	-0.952	Destabilizing	0.012	N	0.473	neutral	N	0.442521436	None	None	N
F/K	0.3574	ambiguous	0.4816	ambiguous	-1.121	Destabilizing	0.016	N	0.601	neutral	None	None	None	None	N
F/L	0.2261	likely_benign	0.318	benign	-0.952	Destabilizing	None	N	0.236	neutral	N	0.364162894	None	None	N
F/M	0.1384	likely_benign	0.1647	benign	-0.877	Destabilizing	0.12	N	0.538	neutral	None	None	None	None	N
F/N	0.1223	likely_benign	0.1349	benign	-1.257	Destabilizing	0.016	N	0.602	neutral	None	None	None	None	N
F/P	0.6094	likely_pathogenic	0.7911	pathogenic	-1.244	Destabilizing	0.136	N	0.695	prob.neutral	None	None	None	None	N
F/Q	0.2296	likely_benign	0.3094	benign	-1.225	Destabilizing	0.072	N	0.693	prob.neutral	None	None	None	None	N
F/R	0.2666	likely_benign	0.372	ambiguous	-0.564	Destabilizing	0.072	N	0.676	prob.neutral	None	None	None	None	N
F/S	0.0598	likely_benign	0.0576	benign	-2.082	Highly Destabilizing	None	N	0.387	neutral	N	0.300739745	None	None	N
F/T	0.0897	likely_benign	0.0941	benign	-1.9	Destabilizing	0.016	N	0.543	neutral	None	None	None	None	N
F/V	0.0682	likely_benign	0.0784	benign	-1.244	Destabilizing	0.012	N	0.487	neutral	N	0.391704703	None	None	N
F/W	0.176	likely_benign	0.2441	benign	-0.137	Destabilizing	0.628	D	0.554	neutral	None	None	None	None	N
F/Y	0.0745	likely_benign	0.0786	benign	-0.405	Destabilizing	0.012	N	0.497	neutral	N	0.391240278	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.