TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28015	84268;84269;84270	chr2:178562089;178562088;178562087	chr2:179426816;179426815;179426814
N2AB	26374	79345;79346;79347	chr2:178562089;178562088;178562087	chr2:179426816;179426815;179426814
N2A	25447	76564;76565;76566	chr2:178562089;178562088;178562087	chr2:179426816;179426815;179426814
N2B	18950	57073;57074;57075	chr2:178562089;178562088;178562087	chr2:179426816;179426815;179426814
Novex-1	19075	57448;57449;57450	chr2:178562089;178562088;178562087	chr2:179426816;179426815;179426814
Novex-2	19142	57649;57650;57651	chr2:178562089;178562088;178562087	chr2:179426816;179426815;179426814
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-142
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.6621
• 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
K/N	rs1457024696	0.335	0.988	N	0.61	0.174	0.0986583533028	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/N	rs1457024696	0.335	0.988	N	0.61	0.174	0.0986583533028	gnomAD-4.0.0	1.59264E-06	None	None	None	None	N	None	0	2.28896E-05	None	0	0	None	0	0	0	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
K/A	0.2111	likely_benign	0.2124	benign	-0.015	Destabilizing	0.968	D	0.561	neutral	None	None	None	None	N
K/C	0.6514	likely_pathogenic	0.656	pathogenic	-0.494	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/D	0.3361	likely_benign	0.3246	benign	-0.165	Destabilizing	0.938	D	0.566	neutral	None	None	None	None	N
K/E	0.1274	likely_benign	0.1295	benign	-0.175	Destabilizing	0.067	N	0.289	neutral	N	0.412358909	None	None	N
K/F	0.7314	likely_pathogenic	0.7271	pathogenic	-0.371	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/G	0.281	likely_benign	0.2846	benign	-0.138	Destabilizing	0.991	D	0.514	neutral	None	None	None	None	N
K/H	0.3037	likely_benign	0.3046	benign	-0.232	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	N
K/I	0.3572	ambiguous	0.3535	ambiguous	0.227	Stabilizing	0.995	D	0.651	neutral	None	None	None	None	N
K/L	0.3048	likely_benign	0.3041	benign	0.227	Stabilizing	0.991	D	0.53	neutral	None	None	None	None	N
K/M	0.2342	likely_benign	0.2316	benign	-0.121	Destabilizing	0.999	D	0.637	neutral	N	0.46335189	None	None	N
K/N	0.2856	likely_benign	0.2766	benign	-0.036	Destabilizing	0.988	D	0.61	neutral	N	0.448799712	None	None	N
K/P	0.302	likely_benign	0.3005	benign	0.17	Stabilizing	0.995	D	0.613	neutral	None	None	None	None	N
K/Q	0.1202	likely_benign	0.1214	benign	-0.155	Destabilizing	0.976	D	0.588	neutral	N	0.452706809	None	None	N
K/R	0.0785	likely_benign	0.0815	benign	-0.111	Destabilizing	0.958	D	0.516	neutral	N	0.484683154	None	None	N
K/S	0.2614	likely_benign	0.2587	benign	-0.42	Destabilizing	0.968	D	0.54	neutral	None	None	None	None	N
K/T	0.1556	likely_benign	0.1522	benign	-0.309	Destabilizing	0.988	D	0.581	neutral	N	0.503711632	None	None	N
K/V	0.2917	likely_benign	0.2873	benign	0.17	Stabilizing	0.995	D	0.583	neutral	None	None	None	None	N
K/W	0.7477	likely_pathogenic	0.7585	pathogenic	-0.476	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/Y	0.5903	likely_pathogenic	0.5904	pathogenic	-0.118	Destabilizing	0.998	D	0.615	neutral	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.