TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15353	46282;46283;46284	chr2:178620464;178620463;178620462	chr2:179485191;179485190;179485189
N2AB	13712	41359;41360;41361	chr2:178620464;178620463;178620462	chr2:179485191;179485190;179485189
N2A	12785	38578;38579;38580	chr2:178620464;178620463;178620462	chr2:179485191;179485190;179485189
N2B	6288	19087;19088;19089	chr2:178620464;178620463;178620462	chr2:179485191;179485190;179485189
Novex-1	6413	19462;19463;19464	chr2:178620464;178620463;178620462	chr2:179485191;179485190;179485189
Novex-2	6480	19663;19664;19665	chr2:178620464;178620463;178620462	chr2:179485191;179485190;179485189
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-105
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.5453
• 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
K/E	rs747996981	0.149	0.998	N	0.479	0.351	0.229264304666	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
K/E	rs747996981	0.149	0.998	N	0.479	0.351	0.229264304666	gnomAD-4.0.0	3.18855E-06	None	None	None	None	N	None	0	4.58127E-05	None	0	0	None	0	0	0	0	0
K/M	None	None	1.0	N	0.538	0.407	0.277317399466	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
K/A	0.4777	ambiguous	0.4013	ambiguous	-0.389	Destabilizing	0.992	D	0.465	neutral	None	None	None	None	N
K/C	0.7565	likely_pathogenic	0.7774	pathogenic	-0.39	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/D	0.565	likely_pathogenic	0.4882	ambiguous	-0.006	Destabilizing	1.0	D	0.531	neutral	None	None	None	None	N
K/E	0.3013	likely_benign	0.2275	benign	0.07	Stabilizing	0.998	D	0.479	neutral	N	0.423561481	None	None	N
K/F	0.8922	likely_pathogenic	0.8664	pathogenic	-0.318	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
K/G	0.4095	ambiguous	0.37	ambiguous	-0.676	Destabilizing	1.0	D	0.43	neutral	None	None	None	None	N
K/H	0.4313	ambiguous	0.4193	ambiguous	-0.931	Destabilizing	1.0	D	0.551	neutral	None	None	None	None	N
K/I	0.6473	likely_pathogenic	0.5483	ambiguous	0.321	Stabilizing	0.995	D	0.503	neutral	None	None	None	None	N
K/L	0.579	likely_pathogenic	0.5139	ambiguous	0.321	Stabilizing	0.983	D	0.445	neutral	None	None	None	None	N
K/M	0.4118	ambiguous	0.3392	benign	0.017	Stabilizing	1.0	D	0.538	neutral	N	0.497852644	None	None	N
K/N	0.4416	ambiguous	0.3575	ambiguous	-0.141	Destabilizing	0.999	D	0.561	neutral	N	0.446564661	None	None	N
K/P	0.7085	likely_pathogenic	0.6668	pathogenic	0.113	Stabilizing	1.0	D	0.523	neutral	None	None	None	None	N
K/Q	0.2034	likely_benign	0.1825	benign	-0.187	Destabilizing	0.999	D	0.564	neutral	N	0.447137507	None	None	N
K/R	0.1027	likely_benign	0.1012	benign	-0.319	Destabilizing	0.998	D	0.463	neutral	N	0.448515497	None	None	N
K/S	0.4891	ambiguous	0.4221	ambiguous	-0.673	Destabilizing	0.996	D	0.475	neutral	None	None	None	None	N
K/T	0.2976	likely_benign	0.2266	benign	-0.411	Destabilizing	0.997	D	0.49	neutral	N	0.44689616	None	None	N
K/V	0.6008	likely_pathogenic	0.5134	ambiguous	0.113	Stabilizing	0.784	D	0.349	neutral	None	None	None	None	N
K/W	0.8693	likely_pathogenic	0.8682	pathogenic	-0.292	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/Y	0.74	likely_pathogenic	0.7036	pathogenic	0.009	Stabilizing	1.0	D	0.54	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.