TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6921	20986;20987;20988	chr2:178725443;178725442;178725441	chr2:179590170;179590169;179590168
N2AB	6604	20035;20036;20037	chr2:178725443;178725442;178725441	chr2:179590170;179590169;179590168
N2A	5677	17254;17255;17256	chr2:178725443;178725442;178725441	chr2:179590170;179590169;179590168
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: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-53
• Domain position: 68
• Structural Position: 149
• Q(SASA): 0.3215
• 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	None	N	0.245	0.144	0.252681307341	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
N/A	0.2012	likely_benign	0.1923	benign	-1.046	Destabilizing	0.007	N	0.551	neutral	None	None	None	None	N
N/C	0.2163	likely_benign	0.225	benign	-0.259	Destabilizing	0.676	D	0.762	deleterious	None	None	None	None	N
N/D	0.1083	likely_benign	0.1039	benign	-0.853	Destabilizing	None	N	0.283	neutral	N	0.420479747	None	None	N
N/E	0.5156	ambiguous	0.5066	ambiguous	-0.64	Destabilizing	0.016	N	0.49	neutral	None	None	None	None	N
N/F	0.4625	ambiguous	0.4729	ambiguous	-0.67	Destabilizing	0.214	N	0.757	deleterious	None	None	None	None	N
N/G	0.2964	likely_benign	0.2775	benign	-1.455	Destabilizing	0.016	N	0.463	neutral	None	None	None	None	N
N/H	0.0914	likely_benign	0.099	benign	-0.811	Destabilizing	None	N	0.369	neutral	N	0.470837649	None	None	N
N/I	0.2372	likely_benign	0.2418	benign	0.043	Stabilizing	0.055	N	0.725	prob.delet.	N	0.506167349	None	None	N
N/K	0.5988	likely_pathogenic	0.6268	pathogenic	-0.073	Destabilizing	0.012	N	0.497	neutral	N	0.505406881	None	None	N
N/L	0.239	likely_benign	0.2393	benign	0.043	Stabilizing	0.031	N	0.636	neutral	None	None	None	None	N
N/M	0.3057	likely_benign	0.2878	benign	0.269	Stabilizing	0.628	D	0.751	deleterious	None	None	None	None	N
N/P	0.8294	likely_pathogenic	0.8161	pathogenic	-0.292	Destabilizing	0.136	N	0.689	prob.neutral	None	None	None	None	N
N/Q	0.4232	ambiguous	0.417	ambiguous	-0.711	Destabilizing	0.072	N	0.519	neutral	None	None	None	None	N
N/R	0.5973	likely_pathogenic	0.6331	pathogenic	-0.201	Destabilizing	0.072	N	0.525	neutral	None	None	None	None	N
N/S	0.0702	likely_benign	0.066	benign	-1.152	Destabilizing	None	N	0.245	neutral	N	0.511164119	None	None	N
N/T	0.1377	likely_benign	0.1315	benign	-0.711	Destabilizing	None	N	0.246	neutral	N	0.498677612	None	None	N
N/V	0.225	likely_benign	0.224	benign	-0.292	Destabilizing	0.072	N	0.651	neutral	None	None	None	None	N
N/W	0.7537	likely_pathogenic	0.7659	pathogenic	-0.429	Destabilizing	0.864	D	0.754	deleterious	None	None	None	None	N
N/Y	0.1543	likely_benign	0.1761	benign	-0.155	Destabilizing	0.093	N	0.746	deleterious	N	0.494557554	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.