TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25029	75310;75311;75312	chr2:178571047;178571046;178571045	chr2:179435774;179435773;179435772
N2AB	23388	70387;70388;70389	chr2:178571047;178571046;178571045	chr2:179435774;179435773;179435772
N2A	22461	67606;67607;67608	chr2:178571047;178571046;178571045	chr2:179435774;179435773;179435772
N2B	15964	48115;48116;48117	chr2:178571047;178571046;178571045	chr2:179435774;179435773;179435772
Novex-1	16089	48490;48491;48492	chr2:178571047;178571046;178571045	chr2:179435774;179435773;179435772
Novex-2	16156	48691;48692;48693	chr2:178571047;178571046;178571045	chr2:179435774;179435773;179435772
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: Fn3-70
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5018
• 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/E	None	None	0.989	N	0.539	0.254	0.251116650651	gnomAD-4.0.0	1.59439E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86618E-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
K/A	0.3495	ambiguous	0.3309	benign	-0.718	Destabilizing	0.983	D	0.596	neutral	None	None	None	None	N
K/C	0.743	likely_pathogenic	0.7235	pathogenic	-0.863	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/D	0.8069	likely_pathogenic	0.7594	pathogenic	-0.646	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
K/E	0.2551	likely_benign	0.2275	benign	-0.497	Destabilizing	0.989	D	0.539	neutral	N	0.488734685	None	None	N
K/F	0.8557	likely_pathogenic	0.8223	pathogenic	-0.404	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/G	0.6481	likely_pathogenic	0.6059	pathogenic	-1.062	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
K/H	0.475	ambiguous	0.4394	ambiguous	-1.078	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/I	0.3925	ambiguous	0.3394	benign	0.183	Stabilizing	0.999	D	0.748	deleterious	N	0.493916811	None	None	N
K/L	0.406	ambiguous	0.3614	ambiguous	0.183	Stabilizing	0.998	D	0.669	neutral	None	None	None	None	N
K/M	0.2503	likely_benign	0.2208	benign	-0.272	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/N	0.6275	likely_pathogenic	0.5667	pathogenic	-0.805	Destabilizing	0.999	D	0.667	neutral	N	0.469571586	None	None	N
K/P	0.3649	ambiguous	0.3517	ambiguous	-0.091	Destabilizing	0.154	N	0.388	neutral	None	None	None	None	N
K/Q	0.1477	likely_benign	0.1361	benign	-0.722	Destabilizing	0.999	D	0.664	neutral	N	0.482232787	None	None	N
K/R	0.0987	likely_benign	0.0975	benign	-0.547	Destabilizing	0.996	D	0.597	neutral	N	0.465551181	None	None	N
K/S	0.5735	likely_pathogenic	0.5242	ambiguous	-1.302	Destabilizing	0.992	D	0.598	neutral	None	None	None	None	N
K/T	0.2847	likely_benign	0.2508	benign	-0.945	Destabilizing	0.997	D	0.714	prob.delet.	N	0.470786127	None	None	N
K/V	0.3589	ambiguous	0.3222	benign	-0.091	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
K/W	0.8706	likely_pathogenic	0.8486	pathogenic	-0.391	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/Y	0.7285	likely_pathogenic	0.6842	pathogenic	-0.113	Destabilizing	0.999	D	0.746	deleterious	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.