TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15019	45280;45281;45282	chr2:178621867;178621866;178621865	chr2:179486594;179486593;179486592
N2AB	13378	40357;40358;40359	chr2:178621867;178621866;178621865	chr2:179486594;179486593;179486592
N2A	12451	37576;37577;37578	chr2:178621867;178621866;178621865	chr2:179486594;179486593;179486592
N2B	5954	18085;18086;18087	chr2:178621867;178621866;178621865	chr2:179486594;179486593;179486592
Novex-1	6079	18460;18461;18462	chr2:178621867;178621866;178621865	chr2:179486594;179486593;179486592
Novex-2	6146	18661;18662;18663	chr2:178621867;178621866;178621865	chr2:179486594;179486593;179486592
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-101
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.645
• 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
R/I	rs1553719573	None	0.996	N	0.579	0.36	0.294206760003	gnomAD-4.0.0	1.36979E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	3.47826E-04	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
R/A	0.4102	ambiguous	0.4048	ambiguous	-0.632	Destabilizing	0.863	D	0.568	neutral	None	None	None	None	N
R/C	0.2541	likely_benign	0.2295	benign	-0.644	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
R/D	0.761	likely_pathogenic	0.7557	pathogenic	0.02	Stabilizing	0.969	D	0.583	neutral	None	None	None	None	N
R/E	0.3795	ambiguous	0.3685	ambiguous	0.102	Stabilizing	0.863	D	0.615	neutral	None	None	None	None	N
R/F	0.6384	likely_pathogenic	0.6294	pathogenic	-0.752	Destabilizing	0.997	D	0.573	neutral	None	None	None	None	N
R/G	0.3029	likely_benign	0.3188	benign	-0.864	Destabilizing	0.959	D	0.565	neutral	N	0.45131756	None	None	N
R/H	0.1286	likely_benign	0.1237	benign	-1.205	Destabilizing	0.997	D	0.607	neutral	None	None	None	None	N
R/I	0.3101	likely_benign	0.3155	benign	-0.036	Destabilizing	0.996	D	0.579	neutral	N	0.473467298	None	None	N
R/K	0.104	likely_benign	0.1031	benign	-0.575	Destabilizing	0.021	N	0.209	neutral	N	0.370015021	None	None	N
R/L	0.3352	likely_benign	0.3207	benign	-0.036	Destabilizing	0.969	D	0.565	neutral	None	None	None	None	N
R/M	0.3163	likely_benign	0.3203	benign	-0.311	Destabilizing	0.997	D	0.585	neutral	None	None	None	None	N
R/N	0.614	likely_pathogenic	0.617	pathogenic	-0.127	Destabilizing	0.969	D	0.602	neutral	None	None	None	None	N
R/P	0.8713	likely_pathogenic	0.8664	pathogenic	-0.215	Destabilizing	0.997	D	0.592	neutral	None	None	None	None	N
R/Q	0.1092	likely_benign	0.11	benign	-0.34	Destabilizing	0.939	D	0.613	neutral	None	None	None	None	N
R/S	0.4669	ambiguous	0.4633	ambiguous	-0.815	Destabilizing	0.92	D	0.57	neutral	N	0.438154726	None	None	N
R/T	0.2401	likely_benign	0.2344	benign	-0.578	Destabilizing	0.959	D	0.57	neutral	N	0.445165411	None	None	N
R/V	0.3749	ambiguous	0.3692	ambiguous	-0.215	Destabilizing	0.991	D	0.569	neutral	None	None	None	None	N
R/W	0.2797	likely_benign	0.2791	benign	-0.558	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
R/Y	0.5231	ambiguous	0.5218	ambiguous	-0.217	Destabilizing	0.997	D	0.597	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.