TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9672	29239;29240;29241	chr2:178707553;178707552;178707551	chr2:179572280;179572279;179572278
N2AB	9355	28288;28289;28290	chr2:178707553;178707552;178707551	chr2:179572280;179572279;179572278
N2A	8428	25507;25508;25509	chr2:178707553;178707552;178707551	chr2:179572280;179572279;179572278
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-82
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3686
• 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
T/I	rs769996978	0.007	0.003	None	0.331	0.198	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	2.34E-05	0
T/I	rs769996978	0.007	0.003	None	0.331	0.198	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	2.94E-05	0	0
T/I	rs769996978	0.007	0.003	None	0.331	0.198	None	gnomAD-4.0.0	6.07434E-05	None	None	None	None	N	None	4.00481E-05	0	None	0	0	None	0	0	7.37563E-05	0	1.28115E-04

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
T/A	0.1033	likely_benign	0.1039	benign	-0.913	Destabilizing	None	N	0.2	neutral	None	None	None	None	N
T/C	0.615	likely_pathogenic	0.5942	pathogenic	-0.434	Destabilizing	0.883	D	0.559	neutral	None	None	None	None	N
T/D	0.6599	likely_pathogenic	0.554	ambiguous	-0.089	Destabilizing	0.22	N	0.545	neutral	None	None	None	None	N
T/E	0.5788	likely_pathogenic	0.4385	ambiguous	-0.081	Destabilizing	0.124	N	0.517	neutral	None	None	None	None	N
T/F	0.2722	likely_benign	0.2577	benign	-0.94	Destabilizing	0.001	N	0.446	neutral	None	None	None	None	N
T/G	0.3867	ambiguous	0.3716	ambiguous	-1.179	Destabilizing	0.055	N	0.545	neutral	None	None	None	None	N
T/H	0.4111	ambiguous	0.3551	ambiguous	-1.349	Destabilizing	0.667	D	0.586	neutral	None	None	None	None	N
T/I	0.2347	likely_benign	0.2041	benign	-0.291	Destabilizing	0.003	N	0.331	neutral	None	None	None	None	N
T/K	0.494	ambiguous	0.3418	ambiguous	-0.73	Destabilizing	0.124	N	0.531	neutral	None	None	None	None	N
T/L	0.1563	likely_benign	0.1478	benign	-0.291	Destabilizing	0.055	N	0.463	neutral	None	None	None	None	N
T/M	0.1097	likely_benign	0.1034	benign	-0.048	Destabilizing	0.667	D	0.561	neutral	None	None	None	None	N
T/N	0.188	likely_benign	0.1868	benign	-0.642	Destabilizing	0.096	N	0.525	neutral	None	None	None	None	N
T/P	0.5495	ambiguous	0.4594	ambiguous	-0.466	Destabilizing	0.602	D	0.585	neutral	None	None	None	None	N
T/Q	0.3927	ambiguous	0.3178	benign	-0.761	Destabilizing	0.497	N	0.579	neutral	None	None	None	None	N
T/R	0.4116	ambiguous	0.2654	benign	-0.49	Destabilizing	0.497	N	0.587	neutral	None	None	None	None	N
T/S	0.1183	likely_benign	0.1227	benign	-0.947	Destabilizing	None	N	0.227	neutral	None	None	None	None	N
T/V	0.167	likely_benign	0.1653	benign	-0.466	Destabilizing	0.055	N	0.484	neutral	None	None	None	None	N
T/W	0.7587	likely_pathogenic	0.713	pathogenic	-0.877	Destabilizing	0.958	D	0.597	neutral	None	None	None	None	N
T/Y	0.3754	ambiguous	0.3541	ambiguous	-0.66	Destabilizing	0.331	N	0.615	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.