TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31860	95803;95804;95805	chr2:178545532;178545531;178545530	chr2:179410259;179410258;179410257
N2AB	30219	90880;90881;90882	chr2:178545532;178545531;178545530	chr2:179410259;179410258;179410257
N2A	29292	88099;88100;88101	chr2:178545532;178545531;178545530	chr2:179410259;179410258;179410257
N2B	22795	68608;68609;68610	chr2:178545532;178545531;178545530	chr2:179410259;179410258;179410257
Novex-1	22920	68983;68984;68985	chr2:178545532;178545531;178545530	chr2:179410259;179410258;179410257
Novex-2	22987	69184;69185;69186	chr2:178545532;178545531;178545530	chr2:179410259;179410258;179410257
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-120
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.4798
• 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
D/E	None	None	0.134	N	0.167	0.065	0.17948927462	gnomAD-4.0.0	6.84255E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99551E-07	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
D/A	0.1832	likely_benign	0.1887	benign	-0.105	Destabilizing	0.92	D	0.359	neutral	N	0.448197571	None	None	N
D/C	0.6602	likely_pathogenic	0.667	pathogenic	-0.366	Destabilizing	0.999	D	0.465	neutral	None	None	None	None	N
D/E	0.1256	likely_benign	0.128	benign	-0.323	Destabilizing	0.134	N	0.167	neutral	N	0.430611888	None	None	N
D/F	0.6395	likely_pathogenic	0.6194	pathogenic	-0.099	Destabilizing	0.997	D	0.451	neutral	None	None	None	None	N
D/G	0.1611	likely_benign	0.1567	benign	-0.222	Destabilizing	0.92	D	0.357	neutral	N	0.433825552	None	None	N
D/H	0.3481	ambiguous	0.3467	ambiguous	0.607	Stabilizing	0.988	D	0.359	neutral	N	0.426342219	None	None	N
D/I	0.3879	ambiguous	0.396	ambiguous	0.143	Stabilizing	0.982	D	0.489	neutral	None	None	None	None	N
D/K	0.3903	ambiguous	0.4139	ambiguous	0.27	Stabilizing	0.939	D	0.337	neutral	None	None	None	None	N
D/L	0.4396	ambiguous	0.4331	ambiguous	0.143	Stabilizing	0.939	D	0.444	neutral	None	None	None	None	N
D/M	0.5944	likely_pathogenic	0.5798	pathogenic	-0.127	Destabilizing	0.999	D	0.449	neutral	None	None	None	None	N
D/N	0.1091	likely_benign	0.1074	benign	-0.031	Destabilizing	0.134	N	0.206	neutral	N	0.463167024	None	None	N
D/P	0.6866	likely_pathogenic	0.7143	pathogenic	0.079	Stabilizing	0.997	D	0.403	neutral	None	None	None	None	N
D/Q	0.3486	ambiguous	0.3474	ambiguous	-0.019	Destabilizing	0.982	D	0.355	neutral	None	None	None	None	N
D/R	0.4583	ambiguous	0.4721	ambiguous	0.604	Stabilizing	0.982	D	0.449	neutral	None	None	None	None	N
D/S	0.1355	likely_benign	0.1329	benign	-0.135	Destabilizing	0.759	D	0.387	neutral	None	None	None	None	N
D/T	0.214	likely_benign	0.2214	benign	-0.031	Destabilizing	0.079	N	0.174	neutral	None	None	None	None	N
D/V	0.24	likely_benign	0.2502	benign	0.079	Stabilizing	0.92	D	0.442	neutral	N	0.420626968	None	None	N
D/W	0.8815	likely_pathogenic	0.8742	pathogenic	-0.019	Destabilizing	0.999	D	0.54	neutral	None	None	None	None	N
D/Y	0.2897	likely_benign	0.2827	benign	0.131	Stabilizing	0.996	D	0.451	neutral	N	0.495644801	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.