TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8324	25195;25196;25197	chr2:178718036;178718035;178718034	chr2:179582763;179582762;179582761
N2AB	8007	24244;24245;24246	chr2:178718036;178718035;178718034	chr2:179582763;179582762;179582761
N2A	7080	21463;21464;21465	chr2:178718036;178718035;178718034	chr2:179582763;179582762;179582761
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-68
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.5461
• Predicted PPI site: I

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
N/K	rs879030954	None	0.023	N	0.05	0.102	0.126345400529	gnomAD-4.0.0	4.10537E-06	None	None	None	None	I	None	0	2.23614E-05	None	0	0	None	0	0	4.49757E-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
N/A	0.2118	likely_benign	0.2504	benign	-0.619	Destabilizing	0.013	N	0.243	neutral	None	None	None	None	I
N/C	0.3454	ambiguous	0.4106	ambiguous	0.206	Stabilizing	0.005	N	0.283	neutral	None	None	None	None	I
N/D	0.1756	likely_benign	0.1854	benign	0.038	Stabilizing	0.123	N	0.191	neutral	N	0.483668087	None	None	I
N/E	0.4003	ambiguous	0.4363	ambiguous	0.078	Stabilizing	0.236	N	0.174	neutral	None	None	None	None	I
N/F	0.5604	ambiguous	0.6185	pathogenic	-0.583	Destabilizing	0.848	D	0.48	neutral	None	None	None	None	I
N/G	0.2116	likely_benign	0.2535	benign	-0.9	Destabilizing	0.437	N	0.183	neutral	None	None	None	None	I
N/H	0.1103	likely_benign	0.1126	benign	-0.747	Destabilizing	0.005	N	0.097	neutral	N	0.483169441	None	None	I
N/I	0.2737	likely_benign	0.3377	benign	0.066	Stabilizing	0.021	N	0.184	neutral	N	0.496810742	None	None	I
N/K	0.3636	ambiguous	0.3905	ambiguous	-0.05	Destabilizing	0.023	N	0.05	neutral	N	0.463850175	None	None	I
N/L	0.2285	likely_benign	0.2723	benign	0.066	Stabilizing	0.003	N	0.145	neutral	None	None	None	None	I
N/M	0.3573	ambiguous	0.4123	ambiguous	0.465	Stabilizing	0.88	D	0.399	neutral	None	None	None	None	I
N/P	0.3347	likely_benign	0.3635	ambiguous	-0.133	Destabilizing	0.476	N	0.451	neutral	None	None	None	None	I
N/Q	0.3	likely_benign	0.3334	benign	-0.577	Destabilizing	0.075	N	0.069	neutral	None	None	None	None	I
N/R	0.3592	ambiguous	0.3835	ambiguous	-0.066	Destabilizing	0.536	D	0.179	neutral	None	None	None	None	I
N/S	0.0704	likely_benign	0.0752	benign	-0.533	Destabilizing	0.001	N	0.046	neutral	N	0.401550923	None	None	I
N/T	0.1256	likely_benign	0.1403	benign	-0.311	Destabilizing	0.098	N	0.203	neutral	N	0.473240449	None	None	I
N/V	0.271	likely_benign	0.3297	benign	-0.133	Destabilizing	0.016	N	0.332	neutral	None	None	None	None	I
N/W	0.7413	likely_pathogenic	0.7705	pathogenic	-0.398	Destabilizing	0.998	D	0.375	neutral	None	None	None	None	I
N/Y	0.1892	likely_benign	0.2103	benign	-0.187	Destabilizing	0.808	D	0.472	neutral	N	0.49323172	None	None	I

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.