TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17280	52063;52064;52065	chr2:178609472;178609471;178609470	chr2:179474199;179474198;179474197
N2AB	15639	47140;47141;47142	chr2:178609472;178609471;178609470	chr2:179474199;179474198;179474197
N2A	14712	44359;44360;44361	chr2:178609472;178609471;178609470	chr2:179474199;179474198;179474197
N2B	8215	24868;24869;24870	chr2:178609472;178609471;178609470	chr2:179474199;179474198;179474197
Novex-1	8340	25243;25244;25245	chr2:178609472;178609471;178609470	chr2:179474199;179474198;179474197
Novex-2	8407	25444;25445;25446	chr2:178609472;178609471;178609470	chr2:179474199;179474198;179474197
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-112
• Domain position: 30
• Structural Position: 47
• Q(SASA): 0.2117
• 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
T/K	rs1225457381	-0.116	0.997	D	0.777	0.423	0.490489133298	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
T/K	rs1225457381	-0.116	0.997	D	0.777	0.423	0.490489133298	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/K	rs1225457381	-0.116	0.997	D	0.777	0.423	0.490489133298	gnomAD-4.0.0	6.58432E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47223E-05	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
T/A	0.1513	likely_benign	0.1382	benign	-0.792	Destabilizing	0.76	D	0.682	prob.neutral	N	0.491404002	None	None	N
T/C	0.4442	ambiguous	0.4574	ambiguous	-0.509	Destabilizing	0.252	N	0.625	neutral	None	None	None	None	N
T/D	0.6595	likely_pathogenic	0.6165	pathogenic	-0.425	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
T/E	0.407	ambiguous	0.3832	ambiguous	-0.305	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
T/F	0.3019	likely_benign	0.2926	benign	-0.523	Destabilizing	0.993	D	0.837	deleterious	None	None	None	None	N
T/G	0.4872	ambiguous	0.4687	ambiguous	-1.156	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	N
T/H	0.24	likely_benign	0.2378	benign	-1.252	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
T/I	0.1979	likely_benign	0.1751	benign	0.127	Stabilizing	0.885	D	0.761	deleterious	N	0.488165226	None	None	N
T/K	0.2418	likely_benign	0.2325	benign	-0.53	Destabilizing	0.997	D	0.777	deleterious	D	0.531307318	None	None	N
T/L	0.1543	likely_benign	0.1429	benign	0.127	Stabilizing	0.91	D	0.736	prob.delet.	None	None	None	None	N
T/M	0.1374	likely_benign	0.1348	benign	0.068	Stabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
T/N	0.2343	likely_benign	0.2158	benign	-0.872	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
T/P	0.903	likely_pathogenic	0.8822	pathogenic	-0.146	Destabilizing	0.997	D	0.819	deleterious	D	0.527411929	None	None	N
T/Q	0.2494	likely_benign	0.2453	benign	-0.766	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
T/R	0.1903	likely_benign	0.1905	benign	-0.547	Destabilizing	0.997	D	0.823	deleterious	N	0.496683921	None	None	N
T/S	0.1403	likely_benign	0.1396	benign	-1.156	Destabilizing	0.939	D	0.656	neutral	N	0.519740743	None	None	N
T/V	0.1751	likely_benign	0.1577	benign	-0.146	Destabilizing	0.214	N	0.471	neutral	None	None	None	None	N
T/W	0.6409	likely_pathogenic	0.6447	pathogenic	-0.597	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
T/Y	0.3147	likely_benign	0.3102	benign	-0.267	Destabilizing	0.998	D	0.845	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.