TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28047	84364;84365;84366	chr2:178561993;178561992;178561991	chr2:179426720;179426719;179426718
N2AB	26406	79441;79442;79443	chr2:178561993;178561992;178561991	chr2:179426720;179426719;179426718
N2A	25479	76660;76661;76662	chr2:178561993;178561992;178561991	chr2:179426720;179426719;179426718
N2B	18982	57169;57170;57171	chr2:178561993;178561992;178561991	chr2:179426720;179426719;179426718
Novex-1	19107	57544;57545;57546	chr2:178561993;178561992;178561991	chr2:179426720;179426719;179426718
Novex-2	19174	57745;57746;57747	chr2:178561993;178561992;178561991	chr2:179426720;179426719;179426718
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-142
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.5478
• 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
P/S	rs1390232115	-0.799	None	N	0.209	0.109	0.228597637076	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
P/S	rs1390232115	-0.799	None	N	0.209	0.109	0.228597637076	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85933E-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
P/A	0.1176	likely_benign	0.1234	benign	-1.164	Destabilizing	0.005	N	0.321	neutral	N	0.435663496	None	None	N
P/C	0.5472	ambiguous	0.5831	pathogenic	-0.662	Destabilizing	0.676	D	0.56	neutral	None	None	None	None	N
P/D	0.3417	ambiguous	0.3538	ambiguous	-1.1	Destabilizing	0.016	N	0.453	neutral	None	None	None	None	N
P/E	0.357	ambiguous	0.3692	ambiguous	-1.164	Destabilizing	None	N	0.211	neutral	None	None	None	None	N
P/F	0.5626	ambiguous	0.6029	pathogenic	-1.102	Destabilizing	0.214	N	0.599	neutral	None	None	None	None	N
P/G	0.2953	likely_benign	0.3155	benign	-1.41	Destabilizing	None	N	0.307	neutral	None	None	None	None	N
P/H	0.2808	likely_benign	0.3157	benign	-1.022	Destabilizing	None	N	0.349	neutral	N	0.441013388	None	None	N
P/I	0.4877	ambiguous	0.5036	ambiguous	-0.615	Destabilizing	0.038	N	0.582	neutral	None	None	None	None	N
P/K	0.3661	ambiguous	0.378	ambiguous	-1.006	Destabilizing	0.016	N	0.467	neutral	None	None	None	None	N
P/L	0.2072	likely_benign	0.2288	benign	-0.615	Destabilizing	None	N	0.365	neutral	N	0.470546861	None	None	N
P/M	0.4475	ambiguous	0.4723	ambiguous	-0.391	Destabilizing	0.214	N	0.56	neutral	None	None	None	None	N
P/N	0.2554	likely_benign	0.2631	benign	-0.64	Destabilizing	0.038	N	0.572	neutral	None	None	None	None	N
P/Q	0.2578	likely_benign	0.2821	benign	-0.888	Destabilizing	0.072	N	0.575	neutral	None	None	None	None	N
P/R	0.2939	likely_benign	0.3328	benign	-0.424	Destabilizing	0.055	N	0.614	neutral	N	0.432335189	None	None	N
P/S	0.1337	likely_benign	0.1426	benign	-1.04	Destabilizing	None	N	0.209	neutral	N	0.372593453	None	None	N
P/T	0.1637	likely_benign	0.1695	benign	-1.004	Destabilizing	0.012	N	0.451	neutral	N	0.372844169	None	None	N
P/V	0.3589	ambiguous	0.3686	ambiguous	-0.763	Destabilizing	0.001	N	0.328	neutral	None	None	None	None	N
P/W	0.7276	likely_pathogenic	0.7763	pathogenic	-1.237	Destabilizing	0.864	D	0.577	neutral	None	None	None	None	N
P/Y	0.5575	ambiguous	0.6055	pathogenic	-0.965	Destabilizing	0.12	N	0.621	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.