TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15640	47143;47144;47145	chr2:178618632;178618631;178618630	chr2:179483359;179483358;179483357
N2AB	13999	42220;42221;42222	chr2:178618632;178618631;178618630	chr2:179483359;179483358;179483357
N2A	13072	39439;39440;39441	chr2:178618632;178618631;178618630	chr2:179483359;179483358;179483357
N2B	6575	19948;19949;19950	chr2:178618632;178618631;178618630	chr2:179483359;179483358;179483357
Novex-1	6700	20323;20324;20325	chr2:178618632;178618631;178618630	chr2:179483359;179483358;179483357
Novex-2	6767	20524;20525;20526	chr2:178618632;178618631;178618630	chr2:179483359;179483358;179483357
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-108
• Domain position: 73
• Structural Position: 159
• Q(SASA): 0.567
• Predicted PPI site: I

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	0.006	N	0.13	0.2	0.20549828249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
Q/A	0.2189	likely_benign	0.2634	benign	-0.49	Destabilizing	0.495	N	0.463	neutral	None	None	None	None	I
Q/C	0.4084	ambiguous	0.5428	ambiguous	-0.009	Destabilizing	0.995	D	0.553	neutral	None	None	None	None	I
Q/D	0.4538	ambiguous	0.5452	ambiguous	-1.021	Destabilizing	0.704	D	0.349	neutral	None	None	None	None	I
Q/E	0.0995	likely_benign	0.1161	benign	-0.941	Destabilizing	0.27	N	0.339	neutral	N	0.49103694	None	None	I
Q/F	0.53	ambiguous	0.62	pathogenic	-0.268	Destabilizing	0.944	D	0.569	neutral	None	None	None	None	I
Q/G	0.2697	likely_benign	0.3298	benign	-0.833	Destabilizing	0.704	D	0.531	neutral	None	None	None	None	I
Q/H	0.141	likely_benign	0.1733	benign	-0.842	Destabilizing	0.006	N	0.235	neutral	N	0.458047838	None	None	I
Q/I	0.3213	likely_benign	0.3803	ambiguous	0.375	Stabilizing	0.944	D	0.578	neutral	None	None	None	None	I
Q/K	0.0851	likely_benign	0.0879	benign	-0.384	Destabilizing	0.002	N	0.152	neutral	N	0.436633482	None	None	I
Q/L	0.1386	likely_benign	0.1872	benign	0.375	Stabilizing	0.642	D	0.535	neutral	N	0.493310231	None	None	I
Q/M	0.3359	likely_benign	0.4087	ambiguous	0.862	Stabilizing	0.981	D	0.495	neutral	None	None	None	None	I
Q/N	0.2653	likely_benign	0.3048	benign	-0.895	Destabilizing	0.704	D	0.346	neutral	None	None	None	None	I
Q/P	0.7771	likely_pathogenic	0.831	pathogenic	0.118	Stabilizing	0.784	D	0.519	neutral	N	0.496040309	None	None	I
Q/R	0.0811	likely_benign	0.0884	benign	-0.297	Destabilizing	0.006	N	0.13	neutral	N	0.433117574	None	None	I
Q/S	0.2184	likely_benign	0.2434	benign	-0.928	Destabilizing	0.495	N	0.381	neutral	None	None	None	None	I
Q/T	0.1575	likely_benign	0.1755	benign	-0.67	Destabilizing	0.704	D	0.495	neutral	None	None	None	None	I
Q/V	0.2205	likely_benign	0.2642	benign	0.118	Stabilizing	0.828	D	0.575	neutral	None	None	None	None	I
Q/W	0.3618	ambiguous	0.4752	ambiguous	-0.198	Destabilizing	0.995	D	0.545	neutral	None	None	None	None	I
Q/Y	0.3404	ambiguous	0.4308	ambiguous	0.063	Stabilizing	0.893	D	0.515	neutral	None	None	None	None	I

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.