TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6420	19483;19484;19485	chr2:178728668;178728667;178728666	chr2:179593395;179593394;179593393
N2AB	6103	18532;18533;18534	chr2:178728668;178728667;178728666	chr2:179593395;179593394;179593393
N2A	5176	15751;15752;15753	chr2:178728668;178728667;178728666	chr2:179593395;179593394;179593393
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-48
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.0905
• 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	None	None	1.0	D	0.727	0.523	0.30921473904	gnomAD-4.0.0	6.84418E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9964E-07	0	0
K/Q	None	None	1.0	N	0.719	0.554	0.357724736475	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/T	None	None	1.0	N	0.767	0.485	0.503002171853	gnomAD-4.0.0	3.18468E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86623E-05	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	0.9485	likely_pathogenic	0.9488	pathogenic	-1.033	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
K/C	0.9463	likely_pathogenic	0.9468	pathogenic	-1.013	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
K/D	0.9916	likely_pathogenic	0.9918	pathogenic	-0.071	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/E	0.8583	likely_pathogenic	0.8497	pathogenic	0.102	Stabilizing	0.999	D	0.629	neutral	D	0.543439729	None	None	N
K/F	0.9649	likely_pathogenic	0.9595	pathogenic	-0.683	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
K/G	0.9723	likely_pathogenic	0.9773	pathogenic	-1.432	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/H	0.637	likely_pathogenic	0.6187	pathogenic	-1.598	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/I	0.8878	likely_pathogenic	0.8663	pathogenic	0.029	Stabilizing	1.0	D	0.869	deleterious	D	0.524068026	None	None	N
K/L	0.8166	likely_pathogenic	0.808	pathogenic	0.029	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/M	0.7321	likely_pathogenic	0.6995	pathogenic	-0.126	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/N	0.9638	likely_pathogenic	0.9582	pathogenic	-0.715	Destabilizing	1.0	D	0.727	prob.delet.	D	0.53166535	None	None	N
K/P	0.9962	likely_pathogenic	0.9966	pathogenic	-0.297	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Q	0.5008	ambiguous	0.4809	ambiguous	-0.672	Destabilizing	1.0	D	0.719	prob.delet.	N	0.510585353	None	None	N
K/R	0.1106	likely_benign	0.1129	benign	-0.562	Destabilizing	0.999	D	0.67	neutral	N	0.51299005	None	None	N
K/S	0.9695	likely_pathogenic	0.9703	pathogenic	-1.526	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
K/T	0.9244	likely_pathogenic	0.9232	pathogenic	-1.109	Destabilizing	1.0	D	0.767	deleterious	N	0.513472189	None	None	N
K/V	0.8713	likely_pathogenic	0.8504	pathogenic	-0.297	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/W	0.921	likely_pathogenic	0.9276	pathogenic	-0.492	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/Y	0.8938	likely_pathogenic	0.8902	pathogenic	-0.204	Destabilizing	1.0	D	0.855	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.