TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25729	77410;77411;77412	chr2:178568947;178568946;178568945	chr2:179433674;179433673;179433672
N2AB	24088	72487;72488;72489	chr2:178568947;178568946;178568945	chr2:179433674;179433673;179433672
N2A	23161	69706;69707;69708	chr2:178568947;178568946;178568945	chr2:179433674;179433673;179433672
N2B	16664	50215;50216;50217	chr2:178568947;178568946;178568945	chr2:179433674;179433673;179433672
Novex-1	16789	50590;50591;50592	chr2:178568947;178568946;178568945	chr2:179433674;179433673;179433672
Novex-2	16856	50791;50792;50793	chr2:178568947;178568946;178568945	chr2:179433674;179433673;179433672
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: Fn3-75
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6526
• Predicted PPI site: I

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	rs531490944	0.243	0.98	N	0.535	0.244	0.247322355667	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.28863E-04	None	0	0	0
K/N	rs531490944	0.243	0.98	N	0.535	0.244	0.247322355667	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
K/N	rs531490944	0.243	0.98	N	0.535	0.244	0.247322355667	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
K/N	rs531490944	0.243	0.98	N	0.535	0.244	0.247322355667	gnomAD-4.0.0	1.36354E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.30622E-04	1.60097E-05

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	0.6646	likely_pathogenic	0.7238	pathogenic	-0.05	Destabilizing	0.97	D	0.602	neutral	None	None	None	None	I
K/C	0.8713	likely_pathogenic	0.8872	pathogenic	-0.261	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
K/D	0.8972	likely_pathogenic	0.9175	pathogenic	0.121	Stabilizing	0.996	D	0.566	neutral	None	None	None	None	I
K/E	0.6059	likely_pathogenic	0.6595	pathogenic	0.149	Stabilizing	0.961	D	0.555	neutral	N	0.466607187	None	None	I
K/F	0.9507	likely_pathogenic	0.962	pathogenic	-0.15	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/G	0.7857	likely_pathogenic	0.8114	pathogenic	-0.282	Destabilizing	0.985	D	0.635	neutral	None	None	None	None	I
K/H	0.5104	ambiguous	0.5522	ambiguous	-0.53	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	I
K/I	0.7034	likely_pathogenic	0.7462	pathogenic	0.491	Stabilizing	0.998	D	0.7	prob.neutral	N	0.517134794	None	None	I
K/L	0.6922	likely_pathogenic	0.7287	pathogenic	0.491	Stabilizing	0.97	D	0.635	neutral	None	None	None	None	I
K/M	0.6193	likely_pathogenic	0.6662	pathogenic	0.211	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	I
K/N	0.7937	likely_pathogenic	0.8321	pathogenic	0.135	Stabilizing	0.98	D	0.535	neutral	N	0.48590781	None	None	I
K/P	0.7183	likely_pathogenic	0.7375	pathogenic	0.34	Stabilizing	0.999	D	0.606	neutral	None	None	None	None	I
K/Q	0.3149	likely_benign	0.3587	ambiguous	None	Stabilizing	0.961	D	0.569	neutral	N	0.500645189	None	None	I
K/R	0.0685	likely_benign	0.0686	benign	-0.1	Destabilizing	0.031	N	0.127	neutral	N	0.422685838	None	None	I
K/S	0.7961	likely_pathogenic	0.8366	pathogenic	-0.378	Destabilizing	0.985	D	0.531	neutral	None	None	None	None	I
K/T	0.5439	ambiguous	0.6051	pathogenic	-0.187	Destabilizing	0.98	D	0.595	neutral	N	0.495892731	None	None	I
K/V	0.6159	likely_pathogenic	0.6679	pathogenic	0.34	Stabilizing	0.996	D	0.615	neutral	None	None	None	None	I
K/W	0.9144	likely_pathogenic	0.9274	pathogenic	-0.146	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
K/Y	0.8741	likely_pathogenic	0.8903	pathogenic	0.194	Stabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I

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.