TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28978	87157;87158;87159	chr2:178558527;178558526;178558525	chr2:179423254;179423253;179423252
N2AB	27337	82234;82235;82236	chr2:178558527;178558526;178558525	chr2:179423254;179423253;179423252
N2A	26410	79453;79454;79455	chr2:178558527;178558526;178558525	chr2:179423254;179423253;179423252
N2B	19913	59962;59963;59964	chr2:178558527;178558526;178558525	chr2:179423254;179423253;179423252
Novex-1	20038	60337;60338;60339	chr2:178558527;178558526;178558525	chr2:179423254;179423253;179423252
Novex-2	20105	60538;60539;60540	chr2:178558527;178558526;178558525	chr2:179423254;179423253;179423252
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: Fn3-99
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1662
• 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/A	None	None	0.052	N	0.511	0.178	0.671759834441	gnomAD-4.0.0	6.15797E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09507E-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
V/A	0.1623	likely_benign	0.1559	benign	-2.568	Highly Destabilizing	0.052	N	0.511	neutral	N	0.471582594	None	None	N
V/C	0.5096	ambiguous	0.5005	ambiguous	-1.928	Destabilizing	0.935	D	0.594	neutral	None	None	None	None	N
V/D	0.4367	ambiguous	0.416	ambiguous	-3.515	Highly Destabilizing	0.484	N	0.631	neutral	N	0.477254134	None	None	N
V/E	0.2843	likely_benign	0.2773	benign	-3.256	Highly Destabilizing	0.555	D	0.625	neutral	None	None	None	None	N
V/F	0.1322	likely_benign	0.123	benign	-1.533	Destabilizing	0.117	N	0.644	neutral	N	0.508552597	None	None	N
V/G	0.3138	likely_benign	0.282	benign	-3.088	Highly Destabilizing	0.484	N	0.653	neutral	N	0.484206347	None	None	N
V/H	0.3173	likely_benign	0.3195	benign	-2.873	Highly Destabilizing	0.935	D	0.628	neutral	None	None	None	None	N
V/I	0.0621	likely_benign	0.0654	benign	-1.061	Destabilizing	None	N	0.202	neutral	N	0.459894645	None	None	N
V/K	0.2495	likely_benign	0.2602	benign	-2.271	Highly Destabilizing	0.555	D	0.627	neutral	None	None	None	None	N
V/L	0.0976	likely_benign	0.1049	benign	-1.061	Destabilizing	None	N	0.243	neutral	N	0.440346092	None	None	N
V/M	0.0909	likely_benign	0.0929	benign	-1.113	Destabilizing	0.38	N	0.63	neutral	None	None	None	None	N
V/N	0.2301	likely_benign	0.2264	benign	-2.756	Highly Destabilizing	0.791	D	0.617	neutral	None	None	None	None	N
V/P	0.9451	likely_pathogenic	0.9495	pathogenic	-1.546	Destabilizing	0.791	D	0.597	neutral	None	None	None	None	N
V/Q	0.225	likely_benign	0.2298	benign	-2.526	Highly Destabilizing	0.791	D	0.599	neutral	None	None	None	None	N
V/R	0.1876	likely_benign	0.2037	benign	-2.066	Highly Destabilizing	0.555	D	0.625	neutral	None	None	None	None	N
V/S	0.1977	likely_benign	0.1869	benign	-3.253	Highly Destabilizing	0.262	N	0.624	neutral	None	None	None	None	N
V/T	0.1197	likely_benign	0.1237	benign	-2.873	Highly Destabilizing	0.149	N	0.595	neutral	None	None	None	None	N
V/W	0.576	likely_pathogenic	0.5776	pathogenic	-2.152	Highly Destabilizing	0.935	D	0.646	neutral	None	None	None	None	N
V/Y	0.3647	ambiguous	0.3487	ambiguous	-1.853	Destabilizing	0.555	D	0.635	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.