TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23322	70189;70190;70191	chr2:178576168;178576167;178576166	chr2:179440895;179440894;179440893
N2AB	21681	65266;65267;65268	chr2:178576168;178576167;178576166	chr2:179440895;179440894;179440893
N2A	20754	62485;62486;62487	chr2:178576168;178576167;178576166	chr2:179440895;179440894;179440893
N2B	14257	42994;42995;42996	chr2:178576168;178576167;178576166	chr2:179440895;179440894;179440893
Novex-1	14382	43369;43370;43371	chr2:178576168;178576167;178576166	chr2:179440895;179440894;179440893
Novex-2	14449	43570;43571;43572	chr2:178576168;178576167;178576166	chr2:179440895;179440894;179440893
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-57
• Domain position: 83
• Structural Position: 114
• Q(SASA): 0.4176
• 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
A/P	None	None	0.989	N	0.448	0.436	0.482429249588	gnomAD-4.0.0	1.59303E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43501E-05	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
A/C	0.344	ambiguous	0.375	ambiguous	-0.702	Destabilizing	0.998	D	0.411	neutral	None	None	None	None	I
A/D	0.546	ambiguous	0.6206	pathogenic	-0.421	Destabilizing	0.728	D	0.516	neutral	None	None	None	None	I
A/E	0.2983	likely_benign	0.3496	ambiguous	-0.578	Destabilizing	0.022	N	0.234	neutral	N	0.512592979	None	None	I
A/F	0.2915	likely_benign	0.3402	ambiguous	-0.849	Destabilizing	0.974	D	0.608	neutral	None	None	None	None	I
A/G	0.2236	likely_benign	0.2329	benign	-0.257	Destabilizing	0.891	D	0.33	neutral	N	0.487369248	None	None	I
A/H	0.4978	ambiguous	0.546	ambiguous	-0.25	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
A/I	0.1408	likely_benign	0.1697	benign	-0.3	Destabilizing	0.728	D	0.448	neutral	None	None	None	None	I
A/K	0.4343	ambiguous	0.4898	ambiguous	-0.55	Destabilizing	0.842	D	0.379	neutral	None	None	None	None	I
A/L	0.1606	likely_benign	0.1932	benign	-0.3	Destabilizing	0.728	D	0.357	neutral	None	None	None	None	I
A/M	0.1554	likely_benign	0.1831	benign	-0.372	Destabilizing	0.993	D	0.453	neutral	None	None	None	None	I
A/N	0.3845	ambiguous	0.445	ambiguous	-0.199	Destabilizing	0.974	D	0.591	neutral	None	None	None	None	I
A/P	0.8706	likely_pathogenic	0.9	pathogenic	-0.239	Destabilizing	0.989	D	0.448	neutral	N	0.511922615	None	None	I
A/Q	0.3459	ambiguous	0.3879	ambiguous	-0.489	Destabilizing	0.949	D	0.44	neutral	None	None	None	None	I
A/R	0.3701	ambiguous	0.4151	ambiguous	-0.072	Destabilizing	0.949	D	0.445	neutral	None	None	None	None	I
A/S	0.1306	likely_benign	0.1431	benign	-0.404	Destabilizing	0.801	D	0.36	neutral	N	0.521079177	None	None	I
A/T	0.1056	likely_benign	0.1167	benign	-0.482	Destabilizing	0.801	D	0.325	neutral	N	0.492804402	None	None	I
A/V	0.0737	likely_benign	0.0802	benign	-0.239	Destabilizing	0.012	N	0.279	neutral	N	0.478115046	None	None	I
A/W	0.7729	likely_pathogenic	0.8237	pathogenic	-0.979	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
A/Y	0.4845	ambiguous	0.5521	ambiguous	-0.628	Destabilizing	0.991	D	0.607	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.