TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7937	24034;24035;24036	chr2:178719683;178719682;178719681	chr2:179584410;179584409;179584408
N2AB	7620	23083;23084;23085	chr2:178719683;178719682;178719681	chr2:179584410;179584409;179584408
N2A	6693	20302;20303;20304	chr2:178719683;178719682;178719681	chr2:179584410;179584409;179584408
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-64
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2697
• 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
I/M	None	None	0.976	N	0.515	0.347	0.4722639086	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	0
I/V	None	None	0.509	D	0.384	0.155	0.602534368506	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
I/A	0.6434	likely_pathogenic	0.6982	pathogenic	-2.122	Highly Destabilizing	0.863	D	0.451	neutral	None	None	None	None	N
I/C	0.7982	likely_pathogenic	0.803	pathogenic	-1.403	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
I/D	0.9306	likely_pathogenic	0.9409	pathogenic	-1.476	Destabilizing	0.991	D	0.623	neutral	None	None	None	None	N
I/E	0.8421	likely_pathogenic	0.8638	pathogenic	-1.396	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	N
I/F	0.1532	likely_benign	0.1619	benign	-1.452	Destabilizing	0.976	D	0.506	neutral	N	0.498218085	None	None	N
I/G	0.8756	likely_pathogenic	0.8936	pathogenic	-2.544	Highly Destabilizing	0.991	D	0.617	neutral	None	None	None	None	N
I/H	0.7171	likely_pathogenic	0.7365	pathogenic	-1.785	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
I/K	0.6157	likely_pathogenic	0.6702	pathogenic	-1.459	Destabilizing	0.982	D	0.621	neutral	None	None	None	None	N
I/L	0.1447	likely_benign	0.1704	benign	-0.985	Destabilizing	0.005	N	0.165	neutral	D	0.526882933	None	None	N
I/M	0.1167	likely_benign	0.1245	benign	-0.783	Destabilizing	0.976	D	0.515	neutral	N	0.492102019	None	None	N
I/N	0.5925	likely_pathogenic	0.6231	pathogenic	-1.373	Destabilizing	0.988	D	0.615	neutral	D	0.533567676	None	None	N
I/P	0.8994	likely_pathogenic	0.9296	pathogenic	-1.335	Destabilizing	0.997	D	0.617	neutral	None	None	None	None	N
I/Q	0.6573	likely_pathogenic	0.6862	pathogenic	-1.442	Destabilizing	0.997	D	0.631	neutral	None	None	None	None	N
I/R	0.5174	ambiguous	0.5656	pathogenic	-0.971	Destabilizing	0.991	D	0.614	neutral	None	None	None	None	N
I/S	0.6075	likely_pathogenic	0.6378	pathogenic	-2.111	Highly Destabilizing	0.852	D	0.505	neutral	N	0.504169567	None	None	N
I/T	0.5312	ambiguous	0.5787	pathogenic	-1.892	Destabilizing	0.134	N	0.33	neutral	N	0.50530843	None	None	N
I/V	0.1028	likely_benign	0.1128	benign	-1.335	Destabilizing	0.509	D	0.384	neutral	D	0.529957737	None	None	N
I/W	0.8079	likely_pathogenic	0.7999	pathogenic	-1.586	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
I/Y	0.5835	likely_pathogenic	0.5891	pathogenic	-1.354	Destabilizing	0.997	D	0.558	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.