TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31648	95167;95168;95169	chr2:178546389;178546388;178546387	chr2:179411116;179411115;179411114
N2AB	30007	90244;90245;90246	chr2:178546389;178546388;178546387	chr2:179411116;179411115;179411114
N2A	29080	87463;87464;87465	chr2:178546389;178546388;178546387	chr2:179411116;179411115;179411114
N2B	22583	67972;67973;67974	chr2:178546389;178546388;178546387	chr2:179411116;179411115;179411114
Novex-1	22708	68347;68348;68349	chr2:178546389;178546388;178546387	chr2:179411116;179411115;179411114
Novex-2	22775	68548;68549;68550	chr2:178546389;178546388;178546387	chr2:179411116;179411115;179411114
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-152
• Domain position: 28
• Structural Position: 47
• Q(SASA): 0.4953
• 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
I/F	rs1409620740	-0.915	None	N	0.157	0.215	0.464528537357	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
I/F	rs1409620740	-0.915	None	N	0.157	0.215	0.464528537357	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	0	0
I/V	None	None	0.047	N	0.27	0.138	0.496299407791	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85838E-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
I/A	0.2343	likely_benign	0.241	benign	-1.83	Destabilizing	0.228	N	0.416	neutral	None	None	None	None	N
I/C	0.4443	ambiguous	0.4553	ambiguous	-0.975	Destabilizing	0.94	D	0.514	neutral	None	None	None	None	N
I/D	0.6442	likely_pathogenic	0.6512	pathogenic	-1.396	Destabilizing	0.816	D	0.575	neutral	None	None	None	None	N
I/E	0.5163	ambiguous	0.5317	ambiguous	-1.305	Destabilizing	0.816	D	0.561	neutral	None	None	None	None	N
I/F	0.097	likely_benign	0.1049	benign	-1.087	Destabilizing	None	N	0.157	neutral	N	0.436146286	None	None	N
I/G	0.5127	ambiguous	0.5288	ambiguous	-2.227	Highly Destabilizing	0.593	D	0.535	neutral	None	None	None	None	N
I/H	0.2906	likely_benign	0.3128	benign	-1.36	Destabilizing	0.716	D	0.519	neutral	None	None	None	None	N
I/K	0.4031	ambiguous	0.4055	ambiguous	-1.256	Destabilizing	0.593	D	0.562	neutral	None	None	None	None	N
I/L	0.1061	likely_benign	0.1075	benign	-0.765	Destabilizing	0.021	N	0.277	neutral	N	0.48024378	None	None	N
I/M	0.1072	likely_benign	0.1077	benign	-0.616	Destabilizing	0.794	D	0.459	neutral	N	0.454558688	None	None	N
I/N	0.2352	likely_benign	0.2365	benign	-1.207	Destabilizing	0.921	D	0.56	neutral	N	0.463831532	None	None	N
I/P	0.9733	likely_pathogenic	0.9698	pathogenic	-1.092	Destabilizing	0.94	D	0.532	neutral	None	None	None	None	N
I/Q	0.32	likely_benign	0.3401	ambiguous	-1.274	Destabilizing	0.94	D	0.531	neutral	None	None	None	None	N
I/R	0.2816	likely_benign	0.2897	benign	-0.749	Destabilizing	0.836	D	0.561	neutral	None	None	None	None	N
I/S	0.1601	likely_benign	0.1656	benign	-1.854	Destabilizing	0.523	D	0.533	neutral	N	0.39196586	None	None	N
I/T	0.1424	likely_benign	0.1409	benign	-1.638	Destabilizing	0.523	D	0.481	neutral	N	0.348871231	None	None	N
I/V	0.077	likely_benign	0.077	benign	-1.092	Destabilizing	0.047	N	0.27	neutral	N	0.436356929	None	None	N
I/W	0.6338	likely_pathogenic	0.6534	pathogenic	-1.246	Destabilizing	0.94	D	0.51	neutral	None	None	None	None	N
I/Y	0.3345	likely_benign	0.3503	ambiguous	-0.997	Destabilizing	0.001	N	0.246	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.