TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17340	52243;52244;52245	chr2:178609292;178609291;178609290	chr2:179474019;179474018;179474017
N2AB	15699	47320;47321;47322	chr2:178609292;178609291;178609290	chr2:179474019;179474018;179474017
N2A	14772	44539;44540;44541	chr2:178609292;178609291;178609290	chr2:179474019;179474018;179474017
N2B	8275	25048;25049;25050	chr2:178609292;178609291;178609290	chr2:179474019;179474018;179474017
Novex-1	8400	25423;25424;25425	chr2:178609292;178609291;178609290	chr2:179474019;179474018;179474017
Novex-2	8467	25624;25625;25626	chr2:178609292;178609291;178609290	chr2:179474019;179474018;179474017
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-112
• Domain position: 90
• Structural Position: 145
• Q(SASA): 0.3777
• 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
L/F	rs770603604	-1.215	0.317	N	0.327	0.06	0.132336055621	gnomAD-2.1.1	1.01923E-04	None	None	None	None	N	None	0	6.96505E-04	None	0	0	None	0	None	0	0	1.76929E-04
L/F	rs770603604	-1.215	0.317	N	0.327	0.06	0.132336055621	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.9698E-04	0	0	0	None	0	0	0	0	0
L/F	rs770603604	-1.215	0.317	N	0.327	0.06	0.132336055621	gnomAD-4.0.0	3.26908E-05	None	None	None	None	N	None	0	4.00641E-04	None	0	0	None	0	0	0	0	5.81159E-05

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
L/A	0.2078	likely_benign	0.2121	benign	-1.656	Destabilizing	0.001	N	0.154	neutral	None	None	None	None	N
L/C	0.337	likely_benign	0.3374	benign	-1.059	Destabilizing	0.555	D	0.369	neutral	None	None	None	None	N
L/D	0.609	likely_pathogenic	0.6185	pathogenic	-0.929	Destabilizing	0.555	D	0.437	neutral	None	None	None	None	N
L/E	0.2501	likely_benign	0.2411	benign	-0.916	Destabilizing	0.555	D	0.413	neutral	None	None	None	None	N
L/F	0.1311	likely_benign	0.1314	benign	-1.121	Destabilizing	0.317	N	0.327	neutral	N	0.48930598	None	None	N
L/G	0.5064	ambiguous	0.5348	ambiguous	-1.988	Destabilizing	0.149	N	0.418	neutral	None	None	None	None	N
L/H	0.2143	likely_benign	0.201	benign	-1.117	Destabilizing	0.915	D	0.408	neutral	N	0.452307817	None	None	N
L/I	0.0639	likely_benign	0.0652	benign	-0.819	Destabilizing	None	N	0.091	neutral	N	0.419446037	None	None	N
L/K	0.1996	likely_benign	0.1984	benign	-1.148	Destabilizing	0.555	D	0.384	neutral	None	None	None	None	N
L/M	0.1059	likely_benign	0.1056	benign	-0.632	Destabilizing	0.38	N	0.398	neutral	None	None	None	None	N
L/N	0.2931	likely_benign	0.312	benign	-1.007	Destabilizing	0.791	D	0.436	neutral	None	None	None	None	N
L/P	0.8754	likely_pathogenic	0.8709	pathogenic	-1.066	Destabilizing	0.484	N	0.435	neutral	N	0.508334458	None	None	N
L/Q	0.1125	likely_benign	0.1057	benign	-1.16	Destabilizing	0.791	D	0.408	neutral	None	None	None	None	N
L/R	0.1651	likely_benign	0.1544	benign	-0.543	Destabilizing	0.484	N	0.406	neutral	N	0.421638193	None	None	N
L/S	0.2166	likely_benign	0.2233	benign	-1.666	Destabilizing	0.081	N	0.365	neutral	None	None	None	None	N
L/T	0.156	likely_benign	0.1562	benign	-1.532	Destabilizing	0.081	N	0.314	neutral	None	None	None	None	N
L/V	0.0669	likely_benign	0.0631	benign	-1.066	Destabilizing	None	N	0.109	neutral	N	0.411903989	None	None	N
L/W	0.364	ambiguous	0.3421	ambiguous	-1.18	Destabilizing	0.935	D	0.459	neutral	None	None	None	None	N
L/Y	0.3308	likely_benign	0.3276	benign	-0.966	Destabilizing	0.555	D	0.373	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.