TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29648	89167;89168;89169	chr2:178554169;178554168;178554167	chr2:179418896;179418895;179418894
N2AB	28007	84244;84245;84246	chr2:178554169;178554168;178554167	chr2:179418896;179418895;179418894
N2A	27080	81463;81464;81465	chr2:178554169;178554168;178554167	chr2:179418896;179418895;179418894
N2B	20583	61972;61973;61974	chr2:178554169;178554168;178554167	chr2:179418896;179418895;179418894
Novex-1	20708	62347;62348;62349	chr2:178554169;178554168;178554167	chr2:179418896;179418895;179418894
Novex-2	20775	62548;62549;62550	chr2:178554169;178554168;178554167	chr2:179418896;179418895;179418894
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-104
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3444
• 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/I	None	None	0.934	N	0.453	0.26	0.599314493506	gnomAD-4.0.0	1.60077E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86776E-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	0.2289	likely_benign	0.2503	benign	-0.64	Destabilizing	0.525	D	0.372	neutral	None	None	None	None	N
N/C	0.2658	likely_benign	0.3028	benign	0.04	Stabilizing	0.998	D	0.397	neutral	None	None	None	None	N
N/D	0.1148	likely_benign	0.1203	benign	-1.008	Destabilizing	0.625	D	0.295	neutral	N	0.403406644	None	None	N
N/E	0.3356	likely_benign	0.3524	ambiguous	-1.009	Destabilizing	0.525	D	0.271	neutral	None	None	None	None	N
N/F	0.4603	ambiguous	0.4963	ambiguous	-1.01	Destabilizing	0.974	D	0.431	neutral	None	None	None	None	N
N/G	0.2491	likely_benign	0.2699	benign	-0.836	Destabilizing	0.688	D	0.313	neutral	None	None	None	None	N
N/H	0.1098	likely_benign	0.1173	benign	-0.894	Destabilizing	0.028	N	0.193	neutral	N	0.502282772	None	None	N
N/I	0.2949	likely_benign	0.3333	benign	-0.191	Destabilizing	0.934	D	0.453	neutral	N	0.480082198	None	None	N
N/K	0.361	ambiguous	0.3806	ambiguous	-0.052	Destabilizing	0.454	N	0.263	neutral	N	0.467965424	None	None	N
N/L	0.2731	likely_benign	0.3016	benign	-0.191	Destabilizing	0.728	D	0.445	neutral	None	None	None	None	N
N/M	0.2996	likely_benign	0.3326	benign	0.523	Stabilizing	0.974	D	0.369	neutral	None	None	None	None	N
N/P	0.8755	likely_pathogenic	0.9046	pathogenic	-0.316	Destabilizing	0.974	D	0.434	neutral	None	None	None	None	N
N/Q	0.2886	likely_benign	0.3096	benign	-0.922	Destabilizing	0.067	N	0.192	neutral	None	None	None	None	N
N/R	0.421	ambiguous	0.4388	ambiguous	0.161	Stabilizing	0.728	D	0.341	neutral	None	None	None	None	N
N/S	0.0916	likely_benign	0.0941	benign	-0.501	Destabilizing	0.062	N	0.059	neutral	N	0.441423528	None	None	N
N/T	0.1082	likely_benign	0.1138	benign	-0.361	Destabilizing	0.051	N	0.099	neutral	N	0.43534013	None	None	N
N/V	0.2919	likely_benign	0.3198	benign	-0.316	Destabilizing	0.728	D	0.481	neutral	None	None	None	None	N
N/W	0.7424	likely_pathogenic	0.7503	pathogenic	-0.875	Destabilizing	0.998	D	0.471	neutral	None	None	None	None	N
N/Y	0.1498	likely_benign	0.1639	benign	-0.586	Destabilizing	0.934	D	0.436	neutral	N	0.483703049	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.