TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28605	86038;86039;86040	chr2:178560319;178560318;178560317	chr2:179425046;179425045;179425044
N2AB	26964	81115;81116;81117	chr2:178560319;178560318;178560317	chr2:179425046;179425045;179425044
N2A	26037	78334;78335;78336	chr2:178560319;178560318;178560317	chr2:179425046;179425045;179425044
N2B	19540	58843;58844;58845	chr2:178560319;178560318;178560317	chr2:179425046;179425045;179425044
Novex-1	19665	59218;59219;59220	chr2:178560319;178560318;178560317	chr2:179425046;179425045;179425044
Novex-2	19732	59419;59420;59421	chr2:178560319;178560318;178560317	chr2:179425046;179425045;179425044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-96
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1332
• 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
V/L	None	None	0.618	N	0.473	0.177	0.303453137403	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
V/A	0.3713	ambiguous	0.3237	benign	-1.551	Destabilizing	0.958	D	0.533	neutral	N	0.465088134	None	None	N
V/C	0.7716	likely_pathogenic	0.7537	pathogenic	-0.906	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
V/D	0.9103	likely_pathogenic	0.8763	pathogenic	-2.098	Highly Destabilizing	0.998	D	0.81	deleterious	N	0.480697174	None	None	N
V/E	0.8092	likely_pathogenic	0.7655	pathogenic	-1.874	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
V/F	0.4272	ambiguous	0.3926	ambiguous	-0.86	Destabilizing	0.988	D	0.755	deleterious	N	0.488841156	None	None	N
V/G	0.5341	ambiguous	0.4699	ambiguous	-2.076	Highly Destabilizing	0.994	D	0.777	deleterious	N	0.509534032	None	None	N
V/H	0.8912	likely_pathogenic	0.8767	pathogenic	-1.958	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/I	0.0853	likely_benign	0.0866	benign	-0.1	Destabilizing	0.067	N	0.332	neutral	N	0.444330547	None	None	N
V/K	0.8306	likely_pathogenic	0.8077	pathogenic	-1.263	Destabilizing	0.995	D	0.75	deleterious	None	None	None	None	N
V/L	0.301	likely_benign	0.2781	benign	-0.1	Destabilizing	0.618	D	0.473	neutral	N	0.507899236	None	None	N
V/M	0.2703	likely_benign	0.2538	benign	-0.11	Destabilizing	0.991	D	0.727	prob.delet.	None	None	None	None	N
V/N	0.7367	likely_pathogenic	0.697	pathogenic	-1.585	Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
V/P	0.9405	likely_pathogenic	0.9107	pathogenic	-0.555	Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
V/Q	0.7279	likely_pathogenic	0.6967	pathogenic	-1.4	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
V/R	0.7668	likely_pathogenic	0.7333	pathogenic	-1.219	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
V/S	0.5165	ambiguous	0.4644	ambiguous	-2.153	Highly Destabilizing	0.995	D	0.744	deleterious	None	None	None	None	N
V/T	0.3968	ambiguous	0.3474	ambiguous	-1.787	Destabilizing	0.968	D	0.626	neutral	None	None	None	None	N
V/W	0.9632	likely_pathogenic	0.9543	pathogenic	-1.442	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
V/Y	0.8462	likely_pathogenic	0.825	pathogenic	-0.954	Destabilizing	0.995	D	0.787	deleterious	None	None	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.