TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3354	10285;10286;10287	chr2:178764231;178764230;178764229	chr2:179628958;179628957;179628956
N2AB	3354	10285;10286;10287	chr2:178764231;178764230;178764229	chr2:179628958;179628957;179628956
N2A	3354	10285;10286;10287	chr2:178764231;178764230;178764229	chr2:179628958;179628957;179628956
N2B	3308	10147;10148;10149	chr2:178764231;178764230;178764229	chr2:179628958;179628957;179628956
Novex-1	3308	10147;10148;10149	chr2:178764231;178764230;178764229	chr2:179628958;179628957;179628956
Novex-2	3308	10147;10148;10149	chr2:178764231;178764230;178764229	chr2:179628958;179628957;179628956
Novex-3	3354	10285;10286;10287	chr2:178764231;178764230;178764229	chr2:179628958;179628957;179628956

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-24
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3137
• 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	rs1487871864	None	None	N	0.209	0.045	0.32980341726	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1487871864	None	None	N	0.209	0.045	0.32980341726	gnomAD-4.0.0	6.56996E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46985E-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	0.0749	likely_benign	0.0681	benign	-1.072	Destabilizing	None	N	0.081	neutral	N	0.495301992	None	None	N
T/C	0.4535	ambiguous	0.344	ambiguous	-0.624	Destabilizing	0.824	D	0.321	neutral	None	None	None	None	N
T/D	0.5267	ambiguous	0.4662	ambiguous	-0.271	Destabilizing	0.38	N	0.338	neutral	None	None	None	None	N
T/E	0.3471	ambiguous	0.3294	benign	-0.24	Destabilizing	0.149	N	0.323	neutral	None	None	None	None	N
T/F	0.3073	likely_benign	0.2481	benign	-1.053	Destabilizing	0.38	N	0.383	neutral	None	None	None	None	N
T/G	0.3767	ambiguous	0.3111	benign	-1.361	Destabilizing	0.081	N	0.381	neutral	None	None	None	None	N
T/H	0.3244	likely_benign	0.2919	benign	-1.587	Destabilizing	0.935	D	0.368	neutral	None	None	None	None	N
T/I	0.1239	likely_benign	0.1082	benign	-0.378	Destabilizing	None	N	0.209	neutral	N	0.485115069	None	None	N
T/K	0.2283	likely_benign	0.2235	benign	-0.736	Destabilizing	0.149	N	0.331	neutral	None	None	None	None	N
T/L	0.1227	likely_benign	0.1033	benign	-0.378	Destabilizing	0.012	N	0.379	neutral	None	None	None	None	N
T/M	0.0909	likely_benign	0.0861	benign	-0.077	Destabilizing	0.38	N	0.335	neutral	None	None	None	None	N
T/N	0.212	likely_benign	0.1883	benign	-0.738	Destabilizing	0.484	N	0.332	neutral	D	0.531368121	None	None	N
T/P	0.5453	ambiguous	0.4855	ambiguous	-0.578	Destabilizing	0.317	N	0.334	neutral	D	0.58353678	None	None	N
T/Q	0.2727	likely_benign	0.2609	benign	-0.872	Destabilizing	0.555	D	0.341	neutral	None	None	None	None	N
T/R	0.1666	likely_benign	0.1576	benign	-0.562	Destabilizing	0.38	N	0.343	neutral	None	None	None	None	N
T/S	0.1541	likely_benign	0.135	benign	-1.083	Destabilizing	0.027	N	0.351	neutral	D	0.549246756	None	None	N
T/V	0.1075	likely_benign	0.0928	benign	-0.578	Destabilizing	0.012	N	0.322	neutral	None	None	None	None	N
T/W	0.7272	likely_pathogenic	0.6357	pathogenic	-0.946	Destabilizing	0.935	D	0.452	neutral	None	None	None	None	N
T/Y	0.3817	ambiguous	0.3384	benign	-0.721	Destabilizing	0.555	D	0.38	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.