TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35647	107164;107165;107166	chr2:178528812;178528811;178528810	chr2:179393539;179393538;179393537
N2AB	34006	102241;102242;102243	chr2:178528812;178528811;178528810	chr2:179393539;179393538;179393537
N2A	33079	99460;99461;99462	chr2:178528812;178528811;178528810	chr2:179393539;179393538;179393537
N2B	26582	79969;79970;79971	chr2:178528812;178528811;178528810	chr2:179393539;179393538;179393537
Novex-1	26707	80344;80345;80346	chr2:178528812;178528811;178528810	chr2:179393539;179393538;179393537
Novex-2	26774	80545;80546;80547	chr2:178528812;178528811;178528810	chr2:179393539;179393538;179393537
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-167
• Domain position: 41
• Structural Position: 70
• Q(SASA): 0.4172
• 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
N/S	None	None	0.999	N	0.494	0.289	0.362758974969	gnomAD-4.0.0	2.05272E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69845E-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	0.4278	ambiguous	0.3851	ambiguous	-0.559	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
N/C	0.7337	likely_pathogenic	0.688	pathogenic	0.252	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
N/D	0.2213	likely_benign	0.1984	benign	0.406	Stabilizing	0.999	D	0.531	neutral	N	0.483014726	None	None	N
N/E	0.6761	likely_pathogenic	0.6241	pathogenic	0.399	Stabilizing	0.999	D	0.578	neutral	None	None	None	None	N
N/F	0.8557	likely_pathogenic	0.8317	pathogenic	-0.837	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
N/G	0.4855	ambiguous	0.4475	ambiguous	-0.76	Destabilizing	0.999	D	0.5	neutral	None	None	None	None	N
N/H	0.2922	likely_benign	0.254	benign	-0.67	Destabilizing	1.0	D	0.581	neutral	N	0.483881518	None	None	N
N/I	0.5362	ambiguous	0.4991	ambiguous	-0.105	Destabilizing	1.0	D	0.689	prob.neutral	N	0.483708159	None	None	N
N/K	0.6281	likely_pathogenic	0.5952	pathogenic	0.16	Stabilizing	1.0	D	0.582	neutral	N	0.482321293	None	None	N
N/L	0.5339	ambiguous	0.4998	ambiguous	-0.105	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
N/M	0.726	likely_pathogenic	0.6776	pathogenic	0.241	Stabilizing	1.0	D	0.586	neutral	None	None	None	None	N
N/P	0.4961	ambiguous	0.4833	ambiguous	-0.229	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
N/Q	0.6674	likely_pathogenic	0.6185	pathogenic	-0.336	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
N/R	0.6559	likely_pathogenic	0.6172	pathogenic	0.181	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
N/S	0.12	likely_benign	0.1099	benign	-0.249	Destabilizing	0.999	D	0.494	neutral	N	0.479894276	None	None	N
N/T	0.3386	likely_benign	0.298	benign	-0.087	Destabilizing	0.999	D	0.576	neutral	N	0.482668009	None	None	N
N/V	0.5274	ambiguous	0.4776	ambiguous	-0.229	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/W	0.9525	likely_pathogenic	0.9398	pathogenic	-0.741	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
N/Y	0.4043	ambiguous	0.3684	ambiguous	-0.494	Destabilizing	1.0	D	0.625	neutral	N	0.484054876	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.