TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18825	56698;56699;56700	chr2:178599320;178599319;178599318	chr2:179464047;179464046;179464045
N2AB	17184	51775;51776;51777	chr2:178599320;178599319;178599318	chr2:179464047;179464046;179464045
N2A	16257	48994;48995;48996	chr2:178599320;178599319;178599318	chr2:179464047;179464046;179464045
N2B	9760	29503;29504;29505	chr2:178599320;178599319;178599318	chr2:179464047;179464046;179464045
Novex-1	9885	29878;29879;29880	chr2:178599320;178599319;178599318	chr2:179464047;179464046;179464045
Novex-2	9952	30079;30080;30081	chr2:178599320;178599319;178599318	chr2:179464047;179464046;179464045
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: Fn3-24
• Domain position: 42
• Structural Position: 43
• Q(SASA): 0.1731
• 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/K	None	None	0.008	N	0.183	0.143	0.226586394389	gnomAD-4.0.0	6.85839E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00513E-07	0	0
R/T	None	None	0.722	N	0.584	0.387	0.337868961071	gnomAD-4.0.0	2.05752E-06	None	None	None	None	N	None	0	0	None	0	2.53229E-05	None	0	0	1.80103E-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
R/A	0.9076	likely_pathogenic	0.9074	pathogenic	-1.832	Destabilizing	0.633	D	0.588	neutral	None	None	None	None	N
R/C	0.4038	ambiguous	0.3358	benign	-1.752	Destabilizing	0.996	D	0.811	deleterious	None	None	None	None	N
R/D	0.992	likely_pathogenic	0.9931	pathogenic	-0.778	Destabilizing	0.633	D	0.643	neutral	None	None	None	None	N
R/E	0.897	likely_pathogenic	0.8892	pathogenic	-0.568	Destabilizing	0.011	N	0.381	neutral	None	None	None	None	N
R/F	0.9677	likely_pathogenic	0.961	pathogenic	-1.09	Destabilizing	0.987	D	0.795	deleterious	None	None	None	None	N
R/G	0.8664	likely_pathogenic	0.8614	pathogenic	-2.189	Highly Destabilizing	0.722	D	0.645	neutral	N	0.501402457	None	None	N
R/H	0.5198	ambiguous	0.469	ambiguous	-2.055	Highly Destabilizing	0.961	D	0.501	neutral	None	None	None	None	N
R/I	0.9166	likely_pathogenic	0.9	pathogenic	-0.806	Destabilizing	0.949	D	0.805	deleterious	N	0.504769819	None	None	N
R/K	0.2346	likely_benign	0.2025	benign	-1.352	Destabilizing	0.008	N	0.183	neutral	N	0.499490396	None	None	N
R/L	0.8348	likely_pathogenic	0.8197	pathogenic	-0.806	Destabilizing	0.775	D	0.653	neutral	None	None	None	None	N
R/M	0.7706	likely_pathogenic	0.7229	pathogenic	-1.268	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	N
R/N	0.9758	likely_pathogenic	0.9738	pathogenic	-1.241	Destabilizing	0.775	D	0.469	neutral	None	None	None	None	N
R/P	0.9978	likely_pathogenic	0.9981	pathogenic	-1.135	Destabilizing	0.961	D	0.747	deleterious	None	None	None	None	N
R/Q	0.2597	likely_benign	0.2279	benign	-1.134	Destabilizing	0.633	D	0.478	neutral	None	None	None	None	N
R/S	0.9599	likely_pathogenic	0.9581	pathogenic	-2.145	Highly Destabilizing	0.565	D	0.553	neutral	N	0.474002131	None	None	N
R/T	0.9008	likely_pathogenic	0.894	pathogenic	-1.72	Destabilizing	0.722	D	0.584	neutral	N	0.491185014	None	None	N
R/V	0.9033	likely_pathogenic	0.8932	pathogenic	-1.135	Destabilizing	0.923	D	0.731	prob.delet.	None	None	None	None	N
R/W	0.7631	likely_pathogenic	0.7433	pathogenic	-0.603	Destabilizing	0.996	D	0.766	deleterious	None	None	None	None	N
R/Y	0.9124	likely_pathogenic	0.8929	pathogenic	-0.44	Destabilizing	0.987	D	0.763	deleterious	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.