TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24981	75166;75167;75168	chr2:178571191;178571190;178571189	chr2:179435918;179435917;179435916
N2AB	23340	70243;70244;70245	chr2:178571191;178571190;178571189	chr2:179435918;179435917;179435916
N2A	22413	67462;67463;67464	chr2:178571191;178571190;178571189	chr2:179435918;179435917;179435916
N2B	15916	47971;47972;47973	chr2:178571191;178571190;178571189	chr2:179435918;179435917;179435916
Novex-1	16041	48346;48347;48348	chr2:178571191;178571190;178571189	chr2:179435918;179435917;179435916
Novex-2	16108	48547;48548;48549	chr2:178571191;178571190;178571189	chr2:179435918;179435917;179435916
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: Fn3-69
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1297
• 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	0.999	N	0.665	0.543	0.340510301474	gnomAD-4.0.0	6.84321E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99575E-07	0	0
F/V	rs1559399002	None	1.0	N	0.671	0.557	0.768676903783	gnomAD-4.0.0	6.84321E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65711E-05

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	0.9953	likely_pathogenic	0.9956	pathogenic	-3.123	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
F/C	0.9167	likely_pathogenic	0.9235	pathogenic	-1.391	Destabilizing	1.0	D	0.811	deleterious	D	0.556683636	None	None	N
F/D	0.9987	likely_pathogenic	0.9984	pathogenic	-3.677	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
F/E	0.9991	likely_pathogenic	0.999	pathogenic	-3.448	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
F/G	0.9961	likely_pathogenic	0.996	pathogenic	-3.544	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
F/H	0.9565	likely_pathogenic	0.9468	pathogenic	-2.46	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
F/I	0.8991	likely_pathogenic	0.9217	pathogenic	-1.705	Destabilizing	1.0	D	0.75	deleterious	N	0.486754469	None	None	N
F/K	0.9991	likely_pathogenic	0.9989	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
F/L	0.9881	likely_pathogenic	0.9899	pathogenic	-1.705	Destabilizing	0.999	D	0.665	neutral	N	0.507772013	None	None	N
F/M	0.9461	likely_pathogenic	0.9511	pathogenic	-1.267	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
F/N	0.9901	likely_pathogenic	0.9891	pathogenic	-2.893	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9999	pathogenic	-2.197	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
F/Q	0.9979	likely_pathogenic	0.9975	pathogenic	-2.741	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
F/R	0.9979	likely_pathogenic	0.9975	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
F/S	0.9925	likely_pathogenic	0.9928	pathogenic	-3.28	Highly Destabilizing	1.0	D	0.803	deleterious	D	0.556683636	None	None	N
F/T	0.9953	likely_pathogenic	0.9954	pathogenic	-2.939	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
F/V	0.9153	likely_pathogenic	0.9336	pathogenic	-2.197	Highly Destabilizing	1.0	D	0.671	neutral	N	0.490687581	None	None	N
F/W	0.7699	likely_pathogenic	0.7598	pathogenic	-0.757	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
F/Y	0.2197	likely_benign	0.2194	benign	-1.286	Destabilizing	0.999	D	0.566	neutral	D	0.526143854	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.