TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6698	20317;20318;20319	chr2:178727273;178727272;178727271	chr2:179592000;179591999;179591998
N2AB	6381	19366;19367;19368	chr2:178727273;178727272;178727271	chr2:179592000;179591999;179591998
N2A	5454	16585;16586;16587	chr2:178727273;178727272;178727271	chr2:179592000;179591999;179591998
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-51
• Domain position: 32
• Structural Position: 45
• Q(SASA): 0.7025
• 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
R/K	None	None	None	N	0.137	0.093	0.176091768786	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.2536	likely_benign	0.2646	benign	-0.085	Destabilizing	0.035	N	0.459	neutral	None	None	None	None	I
R/C	0.2259	likely_benign	0.2383	benign	-0.296	Destabilizing	0.935	D	0.503	neutral	None	None	None	None	I
R/D	0.4357	ambiguous	0.4166	ambiguous	-0.099	Destabilizing	0.149	N	0.57	neutral	None	None	None	None	I
R/E	0.2283	likely_benign	0.2234	benign	-0.015	Destabilizing	0.035	N	0.477	neutral	None	None	None	None	I
R/F	0.5185	ambiguous	0.5414	ambiguous	-0.17	Destabilizing	0.791	D	0.531	neutral	None	None	None	None	I
R/G	0.1849	likely_benign	0.1911	benign	-0.316	Destabilizing	0.117	N	0.544	neutral	N	0.466199834	None	None	I
R/H	0.0858	likely_benign	0.0852	benign	-0.724	Destabilizing	0.38	N	0.547	neutral	None	None	None	None	I
R/I	0.2544	likely_benign	0.2574	benign	0.497	Stabilizing	0.317	N	0.566	neutral	N	0.462159451	None	None	I
R/K	0.0808	likely_benign	0.0786	benign	-0.233	Destabilizing	None	N	0.137	neutral	N	0.355741275	None	None	I
R/L	0.2017	likely_benign	0.2212	benign	0.497	Stabilizing	0.149	N	0.549	neutral	None	None	None	None	I
R/M	0.2321	likely_benign	0.2354	benign	-0.013	Destabilizing	0.555	D	0.553	neutral	None	None	None	None	I
R/N	0.3369	likely_benign	0.3321	benign	-0.014	Destabilizing	0.149	N	0.501	neutral	None	None	None	None	I
R/P	0.7249	likely_pathogenic	0.7152	pathogenic	0.325	Stabilizing	0.262	N	0.601	neutral	None	None	None	None	I
R/Q	0.0884	likely_benign	0.0879	benign	-0.092	Destabilizing	0.001	N	0.258	neutral	None	None	None	None	I
R/S	0.2632	likely_benign	0.2622	benign	-0.404	Destabilizing	0.027	N	0.497	neutral	N	0.40301236	None	None	I
R/T	0.1312	likely_benign	0.1316	benign	-0.173	Destabilizing	0.002	N	0.276	neutral	N	0.411575915	None	None	I
R/V	0.295	likely_benign	0.3022	benign	0.325	Stabilizing	0.149	N	0.565	neutral	None	None	None	None	I
R/W	0.1911	likely_benign	0.1983	benign	-0.146	Destabilizing	0.935	D	0.513	neutral	None	None	None	None	I
R/Y	0.3724	ambiguous	0.385	ambiguous	0.233	Stabilizing	0.555	D	0.559	neutral	None	None	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.