TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8019	24280;24281;24282	chr2:178719335;178719334;178719333	chr2:179584062;179584061;179584060
N2AB	7702	23329;23330;23331	chr2:178719335;178719334;178719333	chr2:179584062;179584061;179584060
N2A	6775	20548;20549;20550	chr2:178719335;178719334;178719333	chr2:179584062;179584061;179584060
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-65
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2002
• 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	rs1404511467	None	0.27	N	0.42	0.247	0.29385284311	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	0.7199	likely_pathogenic	0.8624	pathogenic	-2.295	Highly Destabilizing	0.329	N	0.494	neutral	None	None	None	None	N
F/C	0.486	ambiguous	0.6279	pathogenic	-1.195	Destabilizing	0.993	D	0.577	neutral	N	0.502286332	None	None	N
F/D	0.8613	likely_pathogenic	0.9386	pathogenic	-0.985	Destabilizing	0.543	D	0.542	neutral	None	None	None	None	N
F/E	0.8249	likely_pathogenic	0.9166	pathogenic	-0.906	Destabilizing	0.031	N	0.456	neutral	None	None	None	None	N
F/G	0.8335	likely_pathogenic	0.9203	pathogenic	-2.626	Highly Destabilizing	0.704	D	0.545	neutral	None	None	None	None	N
F/H	0.4349	ambiguous	0.5689	pathogenic	-0.898	Destabilizing	0.893	D	0.55	neutral	None	None	None	None	N
F/I	0.3145	likely_benign	0.4472	ambiguous	-1.301	Destabilizing	0.642	D	0.461	neutral	N	0.506600009	None	None	N
F/K	0.7112	likely_pathogenic	0.8376	pathogenic	-1.048	Destabilizing	0.543	D	0.544	neutral	None	None	None	None	N
F/L	0.8321	likely_pathogenic	0.9055	pathogenic	-1.301	Destabilizing	0.27	N	0.42	neutral	N	0.428560513	None	None	N
F/M	0.5812	likely_pathogenic	0.7104	pathogenic	-1.001	Destabilizing	0.981	D	0.509	neutral	None	None	None	None	N
F/N	0.6387	likely_pathogenic	0.7796	pathogenic	-1.014	Destabilizing	0.704	D	0.585	neutral	None	None	None	None	N
F/P	0.9982	likely_pathogenic	0.9992	pathogenic	-1.626	Destabilizing	0.944	D	0.61	neutral	None	None	None	None	N
F/Q	0.667	likely_pathogenic	0.805	pathogenic	-1.163	Destabilizing	0.085	N	0.507	neutral	None	None	None	None	N
F/R	0.5745	likely_pathogenic	0.7165	pathogenic	-0.356	Destabilizing	0.704	D	0.606	neutral	None	None	None	None	N
F/S	0.4732	ambiguous	0.6591	pathogenic	-1.881	Destabilizing	0.065	N	0.425	neutral	N	0.499500678	None	None	N
F/T	0.6289	likely_pathogenic	0.803	pathogenic	-1.71	Destabilizing	0.543	D	0.54	neutral	None	None	None	None	N
F/V	0.3537	ambiguous	0.5116	ambiguous	-1.626	Destabilizing	0.642	D	0.482	neutral	N	0.504714497	None	None	N
F/W	0.4529	ambiguous	0.5551	ambiguous	-0.482	Destabilizing	0.944	D	0.531	neutral	None	None	None	None	N
F/Y	0.1139	likely_benign	0.133	benign	-0.647	Destabilizing	0.002	N	0.191	neutral	N	0.4085506	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.