TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8020	24283;24284;24285	chr2:178719332;178719331;178719330	chr2:179584059;179584058;179584057
N2AB	7703	23332;23333;23334	chr2:178719332;178719331;178719330	chr2:179584059;179584058;179584057
N2A	6776	20551;20552;20553	chr2:178719332;178719331;178719330	chr2:179584059;179584058;179584057
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-65
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.14
• 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
Q/R	None	None	0.012	N	0.421	0.207	0.0297737177859	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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
Q/A	0.2839	likely_benign	0.2874	benign	-0.865	Destabilizing	0.031	N	0.42	neutral	None	None	None	None	N
Q/C	0.406	ambiguous	0.3894	ambiguous	-0.248	Destabilizing	0.864	D	0.665	neutral	None	None	None	None	N
Q/D	0.6186	likely_pathogenic	0.6234	pathogenic	-0.959	Destabilizing	0.136	N	0.459	neutral	None	None	None	None	N
Q/E	0.1255	likely_benign	0.1306	benign	-0.826	Destabilizing	0.024	N	0.393	neutral	N	0.465019958	None	None	N
Q/F	0.474	ambiguous	0.481	ambiguous	-0.693	Destabilizing	0.038	N	0.64	neutral	None	None	None	None	N
Q/G	0.3419	ambiguous	0.3571	ambiguous	-1.234	Destabilizing	0.136	N	0.543	neutral	None	None	None	None	N
Q/H	0.1229	likely_benign	0.1248	benign	-1.169	Destabilizing	None	N	0.333	neutral	N	0.33189797	None	None	N
Q/I	0.3155	likely_benign	0.3054	benign	0.092	Stabilizing	0.038	N	0.581	neutral	None	None	None	None	N
Q/K	0.0696	likely_benign	0.0711	benign	-0.31	Destabilizing	None	N	0.127	neutral	N	0.247137572	None	None	N
Q/L	0.0994	likely_benign	0.098	benign	0.092	Stabilizing	None	N	0.389	neutral	N	0.385441667	None	None	N
Q/M	0.3368	likely_benign	0.3244	benign	0.617	Stabilizing	0.12	N	0.549	neutral	None	None	None	None	N
Q/N	0.4261	ambiguous	0.4274	ambiguous	-0.997	Destabilizing	0.072	N	0.463	neutral	None	None	None	None	N
Q/P	0.4762	ambiguous	0.5283	ambiguous	-0.196	Destabilizing	0.266	N	0.611	neutral	N	0.483779077	None	None	N
Q/R	0.0582	likely_benign	0.0618	benign	-0.323	Destabilizing	0.012	N	0.421	neutral	N	0.346536562	None	None	N
Q/S	0.3426	ambiguous	0.3485	ambiguous	-1.133	Destabilizing	0.031	N	0.408	neutral	None	None	None	None	N
Q/T	0.3178	likely_benign	0.3194	benign	-0.795	Destabilizing	0.072	N	0.521	neutral	None	None	None	None	N
Q/V	0.2519	likely_benign	0.2478	benign	-0.196	Destabilizing	0.016	N	0.475	neutral	None	None	None	None	N
Q/W	0.3007	likely_benign	0.311	benign	-0.571	Destabilizing	0.676	D	0.635	neutral	None	None	None	None	N
Q/Y	0.3037	likely_benign	0.3143	benign	-0.29	Destabilizing	None	N	0.345	neutral	None	None	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.