TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13753	41482;41483;41484	chr2:178636470;178636469;178636468	chr2:179501197;179501196;179501195
N2AB	12112	36559;36560;36561	chr2:178636470;178636469;178636468	chr2:179501197;179501196;179501195
N2A	11185	33778;33779;33780	chr2:178636470;178636469;178636468	chr2:179501197;179501196;179501195
N2B	4688	14287;14288;14289	chr2:178636470;178636469;178636468	chr2:179501197;179501196;179501195
Novex-1	4813	14662;14663;14664	chr2:178636470;178636469;178636468	chr2:179501197;179501196;179501195
Novex-2	4880	14863;14864;14865	chr2:178636470;178636469;178636468	chr2:179501197;179501196;179501195
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-87
• Domain position: 70
• Structural Position: 151
• Q(SASA): 0.2505
• 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
A/G	rs1228071677	None	0.896	N	0.509	0.331	0.473853734676	gnomAD-4.0.0	1.59229E-06	None	None	None	None	N	None	0	2.28718E-05	None	0	0	None	0	0	0	0	0
A/S	None	None	0.64	N	0.579	0.103	0.340273420219	gnomAD-4.0.0	1.3688E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-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
A/C	0.819	likely_pathogenic	0.821	pathogenic	-0.877	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	N
A/D	0.8105	likely_pathogenic	0.828	pathogenic	-0.458	Destabilizing	0.968	D	0.663	neutral	N	0.514945922	None	None	N
A/E	0.5752	likely_pathogenic	0.6017	pathogenic	-0.543	Destabilizing	0.976	D	0.601	neutral	None	None	None	None	N
A/F	0.7956	likely_pathogenic	0.8278	pathogenic	-0.938	Destabilizing	0.988	D	0.766	deleterious	None	None	None	None	N
A/G	0.2588	likely_benign	0.2819	benign	-0.825	Destabilizing	0.896	D	0.509	neutral	N	0.513583285	None	None	N
A/H	0.8522	likely_pathogenic	0.8588	pathogenic	-0.881	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
A/I	0.6538	likely_pathogenic	0.6885	pathogenic	-0.329	Destabilizing	0.976	D	0.64	neutral	None	None	None	None	N
A/K	0.7498	likely_pathogenic	0.7862	pathogenic	-0.881	Destabilizing	0.976	D	0.633	neutral	None	None	None	None	N
A/L	0.5916	likely_pathogenic	0.616	pathogenic	-0.329	Destabilizing	0.851	D	0.559	neutral	None	None	None	None	N
A/M	0.5358	ambiguous	0.5682	pathogenic	-0.336	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
A/N	0.6698	likely_pathogenic	0.6793	pathogenic	-0.566	Destabilizing	0.976	D	0.703	prob.neutral	None	None	None	None	N
A/P	0.9703	likely_pathogenic	0.9644	pathogenic	-0.393	Destabilizing	0.984	D	0.681	prob.neutral	D	0.627796164	None	None	N
A/Q	0.5933	likely_pathogenic	0.6011	pathogenic	-0.762	Destabilizing	0.988	D	0.694	prob.neutral	None	None	None	None	N
A/R	0.6452	likely_pathogenic	0.6731	pathogenic	-0.511	Destabilizing	0.988	D	0.681	prob.neutral	None	None	None	None	N
A/S	0.1198	likely_benign	0.1219	benign	-0.934	Destabilizing	0.64	D	0.579	neutral	N	0.482197364	None	None	N
A/T	0.1616	likely_benign	0.1693	benign	-0.918	Destabilizing	0.046	N	0.189	neutral	N	0.48700654	None	None	N
A/V	0.3646	ambiguous	0.397	ambiguous	-0.393	Destabilizing	0.811	D	0.521	neutral	N	0.505525853	None	None	N
A/W	0.9753	likely_pathogenic	0.9775	pathogenic	-1.158	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
A/Y	0.891	likely_pathogenic	0.9036	pathogenic	-0.776	Destabilizing	0.996	D	0.76	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.