TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15610	47053;47054;47055	chr2:178618722;178618721;178618720	chr2:179483449;179483448;179483447
N2AB	13969	42130;42131;42132	chr2:178618722;178618721;178618720	chr2:179483449;179483448;179483447
N2A	13042	39349;39350;39351	chr2:178618722;178618721;178618720	chr2:179483449;179483448;179483447
N2B	6545	19858;19859;19860	chr2:178618722;178618721;178618720	chr2:179483449;179483448;179483447
Novex-1	6670	20233;20234;20235	chr2:178618722;178618721;178618720	chr2:179483449;179483448;179483447
Novex-2	6737	20434;20435;20436	chr2:178618722;178618721;178618720	chr2:179483449;179483448;179483447
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-108
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.4351
• 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/I	rs748293286	-0.067	0.317	N	0.354	0.121	0.346992582518	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.66E-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	0.0557	likely_benign	0.0634	benign	-0.182	Destabilizing	0.027	N	0.235	neutral	N	0.484210524	None	None	N
T/C	0.2166	likely_benign	0.2856	benign	-0.309	Destabilizing	0.824	D	0.361	neutral	None	None	None	None	N
T/D	0.1413	likely_benign	0.1937	benign	0.246	Stabilizing	0.001	N	0.211	neutral	None	None	None	None	N
T/E	0.1152	likely_benign	0.1532	benign	0.159	Stabilizing	0.035	N	0.269	neutral	None	None	None	None	N
T/F	0.139	likely_benign	0.1893	benign	-0.818	Destabilizing	0.555	D	0.381	neutral	None	None	None	None	N
T/G	0.0923	likely_benign	0.1118	benign	-0.256	Destabilizing	0.035	N	0.303	neutral	None	None	None	None	N
T/H	0.1264	likely_benign	0.1591	benign	-0.458	Destabilizing	0.555	D	0.371	neutral	None	None	None	None	N
T/I	0.1005	likely_benign	0.1366	benign	-0.111	Destabilizing	0.317	N	0.354	neutral	N	0.486564184	None	None	N
T/K	0.0902	likely_benign	0.1072	benign	-0.212	Destabilizing	0.001	N	0.197	neutral	N	0.435107728	None	None	N
T/L	0.0711	likely_benign	0.0829	benign	-0.111	Destabilizing	0.149	N	0.273	neutral	None	None	None	None	N
T/M	0.0808	likely_benign	0.096	benign	-0.108	Destabilizing	0.791	D	0.35	neutral	None	None	None	None	N
T/N	0.0706	likely_benign	0.0804	benign	-0.044	Destabilizing	0.081	N	0.165	neutral	None	None	None	None	N
T/P	0.0586	likely_benign	0.0667	benign	-0.109	Destabilizing	0.117	N	0.345	neutral	N	0.484499307	None	None	N
T/Q	0.0989	likely_benign	0.123	benign	-0.233	Destabilizing	0.38	N	0.342	neutral	None	None	None	None	N
T/R	0.089	likely_benign	0.1068	benign	0.034	Stabilizing	0.062	N	0.325	neutral	N	0.485538884	None	None	N
T/S	0.0642	likely_benign	0.0729	benign	-0.23	Destabilizing	None	N	0.144	neutral	N	0.42637871	None	None	N
T/V	0.0871	likely_benign	0.1098	benign	-0.109	Destabilizing	0.149	N	0.167	neutral	None	None	None	None	N
T/W	0.3069	likely_benign	0.3848	ambiguous	-0.892	Destabilizing	0.935	D	0.433	neutral	None	None	None	None	N
T/Y	0.1433	likely_benign	0.1862	benign	-0.566	Destabilizing	0.555	D	0.379	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.