TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5648	17167;17168;17169	chr2:178731933;178731932;178731931	chr2:179596660;179596659;179596658
N2AB	5331	16216;16217;16218	chr2:178731933;178731932;178731931	chr2:179596660;179596659;179596658
N2A	4404	13435;13436;13437	chr2:178731933;178731932;178731931	chr2:179596660;179596659;179596658
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-40
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.0957
• 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
V/I	None	None	0.37	N	0.335	0.26	0.417208245017	gnomAD-4.0.0	6.85476E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16206E-05	0
V/L	rs1451261949	0.338	0.9	N	0.483	0.355	0.478755181577	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.66E-05	0	0
V/L	rs1451261949	0.338	0.9	N	0.483	0.355	0.478755181577	gnomAD-4.0.0	6.85476E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87406E-05	0	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
V/A	0.2784	likely_benign	0.2838	benign	-1.515	Destabilizing	0.948	D	0.482	neutral	N	0.505241012	None	None	N
V/C	0.8696	likely_pathogenic	0.8661	pathogenic	-0.844	Destabilizing	1.0	D	0.571	neutral	None	None	None	None	N
V/D	0.8252	likely_pathogenic	0.835	pathogenic	-1.797	Destabilizing	0.997	D	0.671	neutral	D	0.529180492	None	None	N
V/E	0.7426	likely_pathogenic	0.7531	pathogenic	-1.546	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
V/F	0.394	ambiguous	0.4401	ambiguous	-0.761	Destabilizing	0.997	D	0.603	neutral	N	0.507682422	None	None	N
V/G	0.3285	likely_benign	0.3205	benign	-2.074	Highly Destabilizing	0.121	N	0.467	neutral	N	0.512748561	None	None	N
V/H	0.9111	likely_pathogenic	0.9216	pathogenic	-1.951	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
V/I	0.1061	likely_benign	0.1193	benign	0.047	Stabilizing	0.37	N	0.335	neutral	N	0.494448015	None	None	N
V/K	0.8239	likely_pathogenic	0.8282	pathogenic	-0.984	Destabilizing	0.998	D	0.627	neutral	None	None	None	None	N
V/L	0.4568	ambiguous	0.5121	ambiguous	0.047	Stabilizing	0.9	D	0.483	neutral	N	0.491651627	None	None	N
V/M	0.2875	likely_benign	0.3284	benign	-0.061	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	N
V/N	0.6612	likely_pathogenic	0.6701	pathogenic	-1.349	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
V/P	0.9284	likely_pathogenic	0.9368	pathogenic	-0.446	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
V/Q	0.7768	likely_pathogenic	0.7848	pathogenic	-1.098	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
V/R	0.7959	likely_pathogenic	0.7982	pathogenic	-1.103	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
V/S	0.4539	ambiguous	0.4573	ambiguous	-1.984	Destabilizing	0.995	D	0.623	neutral	None	None	None	None	N
V/T	0.2918	likely_benign	0.3032	benign	-1.579	Destabilizing	0.992	D	0.575	neutral	None	None	None	None	N
V/W	0.9661	likely_pathogenic	0.9695	pathogenic	-1.306	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
V/Y	0.8354	likely_pathogenic	0.8436	pathogenic	-0.828	Destabilizing	0.999	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.