TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6619	20080;20081;20082	chr2:178727723;178727722;178727721	chr2:179592450;179592449;179592448
N2AB	6302	19129;19130;19131	chr2:178727723;178727722;178727721	chr2:179592450;179592449;179592448
N2A	5375	16348;16349;16350	chr2:178727723;178727722;178727721	chr2:179592450;179592449;179592448
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-50
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.427
• 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/E	rs1060500450	0.559	0.052	N	0.279	0.17	0.20549828249	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/E	rs1060500450	0.559	0.052	N	0.279	0.17	0.20549828249	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/E	rs1060500450	0.559	0.052	N	0.279	0.17	0.20549828249	gnomAD-4.0.0	1.1536E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.15532E-05	0	0
K/T	rs368720026	-0.275	None	N	0.109	0.105	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	1.65728E-04
K/T	rs368720026	-0.275	None	N	0.109	0.105	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	1.93087E-04	6.56E-05	0	0	0	None	0	0	0	0	0
K/T	rs368720026	-0.275	None	N	0.109	0.105	None	gnomAD-4.0.0	1.79463E-05	None	None	None	None	N	None	1.69279E-04	5.08613E-05	None	0	0	None	0	0	2.39479E-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
K/A	0.1661	likely_benign	0.1933	benign	0.006	Stabilizing	0.035	N	0.267	neutral	None	None	None	None	N
K/C	0.5926	likely_pathogenic	0.6933	pathogenic	-0.171	Destabilizing	0.824	D	0.421	neutral	None	None	None	None	N
K/D	0.2463	likely_benign	0.3285	benign	0.232	Stabilizing	0.081	N	0.309	neutral	None	None	None	None	N
K/E	0.1078	likely_benign	0.148	benign	0.257	Stabilizing	0.052	N	0.279	neutral	N	0.498980603	None	None	N
K/F	0.6051	likely_pathogenic	0.6773	pathogenic	-0.126	Destabilizing	0.555	D	0.431	neutral	None	None	None	None	N
K/G	0.2186	likely_benign	0.2764	benign	-0.216	Destabilizing	0.035	N	0.287	neutral	None	None	None	None	N
K/H	0.2169	likely_benign	0.254	benign	-0.467	Destabilizing	0.555	D	0.385	neutral	None	None	None	None	N
K/I	0.2834	likely_benign	0.3291	benign	0.516	Stabilizing	0.188	N	0.463	neutral	N	0.495825655	None	None	N
K/L	0.2524	likely_benign	0.2939	benign	0.516	Stabilizing	0.081	N	0.311	neutral	None	None	None	None	N
K/M	0.189	likely_benign	0.2201	benign	0.223	Stabilizing	0.555	D	0.381	neutral	None	None	None	None	N
K/N	0.1868	likely_benign	0.2298	benign	0.267	Stabilizing	None	N	0.076	neutral	N	0.457517983	None	None	N
K/P	0.4083	ambiguous	0.5287	ambiguous	0.374	Stabilizing	0.262	N	0.432	neutral	None	None	None	None	N
K/Q	0.0986	likely_benign	0.1115	benign	0.143	Stabilizing	0.211	N	0.394	neutral	N	0.514411415	None	None	N
K/R	0.0804	likely_benign	0.0835	benign	-0.015	Destabilizing	0.117	N	0.307	neutral	N	0.397829387	None	None	N
K/S	0.1811	likely_benign	0.2135	benign	-0.244	Destabilizing	0.007	N	0.067	neutral	None	None	None	None	N
K/T	0.1028	likely_benign	0.1067	benign	-0.058	Destabilizing	None	N	0.109	neutral	N	0.462617158	None	None	N
K/V	0.2265	likely_benign	0.2649	benign	0.374	Stabilizing	0.081	N	0.343	neutral	None	None	None	None	N
K/W	0.6666	likely_pathogenic	0.7494	pathogenic	-0.144	Destabilizing	0.935	D	0.469	neutral	None	None	None	None	N
K/Y	0.4474	ambiguous	0.5314	ambiguous	0.207	Stabilizing	0.555	D	0.399	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.