TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2722	8389;8390;8391	chr2:178770628;178770627;178770626	chr2:179635355;179635354;179635353
N2AB	2722	8389;8390;8391	chr2:178770628;178770627;178770626	chr2:179635355;179635354;179635353
N2A	2722	8389;8390;8391	chr2:178770628;178770627;178770626	chr2:179635355;179635354;179635353
N2B	2676	8251;8252;8253	chr2:178770628;178770627;178770626	chr2:179635355;179635354;179635353
Novex-1	2676	8251;8252;8253	chr2:178770628;178770627;178770626	chr2:179635355;179635354;179635353
Novex-2	2676	8251;8252;8253	chr2:178770628;178770627;178770626	chr2:179635355;179635354;179635353
Novex-3	2722	8389;8390;8391	chr2:178770628;178770627;178770626	chr2:179635355;179635354;179635353

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-17
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.4797
• 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/K	None	None	0.997	D	0.446	0.688	0.450733807028	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
Q/P	None	None	0.999	D	0.587	0.849	0.714752477654	gnomAD-4.0.0	6.84147E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99297E-07	0	0
Q/R	rs752069599	0.282	0.997	D	0.495	0.81	0.460438652622	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	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	0.3028	likely_benign	0.3658	ambiguous	-0.307	Destabilizing	0.997	D	0.443	neutral	None	None	None	None	N
Q/C	0.8182	likely_pathogenic	0.865	pathogenic	0.371	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
Q/D	0.441	ambiguous	0.4785	ambiguous	-0.485	Destabilizing	0.997	D	0.499	neutral	None	None	None	None	N
Q/E	0.0848	likely_benign	0.0877	benign	-0.501	Destabilizing	0.992	D	0.403	neutral	N	0.519390386	None	None	N
Q/F	0.8845	likely_pathogenic	0.9114	pathogenic	-0.497	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
Q/G	0.3378	likely_benign	0.4122	ambiguous	-0.534	Destabilizing	0.997	D	0.498	neutral	None	None	None	None	N
Q/H	0.3452	ambiguous	0.3876	ambiguous	-0.676	Destabilizing	0.999	D	0.557	neutral	D	0.6217464	None	None	N
Q/I	0.6979	likely_pathogenic	0.7752	pathogenic	0.217	Stabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
Q/K	0.1228	likely_benign	0.1485	benign	-0.014	Destabilizing	0.997	D	0.446	neutral	D	0.547989389	None	None	N
Q/L	0.2761	likely_benign	0.3415	ambiguous	0.217	Stabilizing	0.997	D	0.498	neutral	D	0.659518378	None	None	N
Q/M	0.4859	ambiguous	0.5397	ambiguous	0.819	Stabilizing	0.999	D	0.557	neutral	None	None	None	None	N
Q/N	0.3673	ambiguous	0.406	ambiguous	-0.322	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	N
Q/P	0.8848	likely_pathogenic	0.9231	pathogenic	0.072	Stabilizing	0.999	D	0.587	neutral	D	0.660154253	None	None	N
Q/R	0.1589	likely_benign	0.1797	benign	0.136	Stabilizing	0.997	D	0.495	neutral	D	0.660824421	None	None	N
Q/S	0.3592	ambiguous	0.4142	ambiguous	-0.313	Destabilizing	0.997	D	0.457	neutral	None	None	None	None	N
Q/T	0.3187	likely_benign	0.3911	ambiguous	-0.172	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
Q/V	0.4876	ambiguous	0.5622	ambiguous	0.072	Stabilizing	0.999	D	0.544	neutral	None	None	None	None	N
Q/W	0.8156	likely_pathogenic	0.835	pathogenic	-0.458	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
Q/Y	0.7116	likely_pathogenic	0.757	pathogenic	-0.192	Destabilizing	0.999	D	0.57	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.