TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19670	59233;59234;59235	chr2:178593200;178593199;178593198	chr2:179457927;179457926;179457925
N2AB	18029	54310;54311;54312	chr2:178593200;178593199;178593198	chr2:179457927;179457926;179457925
N2A	17102	51529;51530;51531	chr2:178593200;178593199;178593198	chr2:179457927;179457926;179457925
N2B	10605	32038;32039;32040	chr2:178593200;178593199;178593198	chr2:179457927;179457926;179457925
Novex-1	10730	32413;32414;32415	chr2:178593200;178593199;178593198	chr2:179457927;179457926;179457925
Novex-2	10797	32614;32615;32616	chr2:178593200;178593199;178593198	chr2:179457927;179457926;179457925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-30
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.7358
• 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
K/N	rs2050621372	None	0.999	N	0.726	0.145	0.197625483188	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	4.76917E-05	0	None	0	0	0	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
K/A	0.3029	likely_benign	0.3311	benign	0.046	Stabilizing	0.997	D	0.63	neutral	None	None	None	None	N
K/C	0.6903	likely_pathogenic	0.7416	pathogenic	-0.31	Destabilizing	1.0	D	0.731	deleterious	None	None	None	None	N
K/D	0.4959	ambiguous	0.5363	ambiguous	-0.018	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
K/E	0.1811	likely_benign	0.1906	benign	-0.009	Destabilizing	0.991	D	0.623	neutral	N	0.443668825	None	None	N
K/F	0.6964	likely_pathogenic	0.7369	pathogenic	-0.167	Destabilizing	1.0	D	0.666	prob.neutral	None	None	None	None	N
K/G	0.4639	ambiguous	0.5025	ambiguous	-0.137	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
K/H	0.3429	ambiguous	0.3745	ambiguous	-0.302	Destabilizing	1.0	D	0.695	prob.delet.	None	None	None	None	N
K/I	0.2831	likely_benign	0.3149	benign	0.449	Stabilizing	1.0	D	0.698	prob.delet.	N	0.472148344	None	None	N
K/L	0.2851	likely_benign	0.3106	benign	0.449	Stabilizing	0.999	D	0.582	neutral	None	None	None	None	N
K/M	0.2315	likely_benign	0.2536	benign	0.082	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/N	0.3908	ambiguous	0.4314	ambiguous	0.133	Stabilizing	0.999	D	0.726	deleterious	N	0.48623031	None	None	N
K/P	0.4448	ambiguous	0.4699	ambiguous	0.342	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/Q	0.1426	likely_benign	0.1485	benign	None	Stabilizing	0.997	D	0.737	deleterious	N	0.490444052	None	None	N
K/R	0.0947	likely_benign	0.0953	benign	-0.055	Destabilizing	0.451	N	0.302	neutral	N	0.496716663	None	None	N
K/S	0.3923	ambiguous	0.4271	ambiguous	-0.3	Destabilizing	0.997	D	0.657	prob.neutral	None	None	None	None	N
K/T	0.1981	likely_benign	0.2153	benign	-0.151	Destabilizing	0.999	D	0.705	prob.delet.	N	0.50760566	None	None	N
K/V	0.2546	likely_benign	0.2784	benign	0.342	Stabilizing	0.999	D	0.703	prob.delet.	None	None	None	None	N
K/W	0.7597	likely_pathogenic	0.8011	pathogenic	-0.227	Destabilizing	1.0	D	0.725	deleterious	None	None	None	None	N
K/Y	0.5719	likely_pathogenic	0.6257	pathogenic	0.126	Stabilizing	1.0	D	0.692	prob.delet.	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.