TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17092	51499;51500;51501	chr2:178610252;178610251;178610250	chr2:179474979;179474978;179474977
N2AB	15451	46576;46577;46578	chr2:178610252;178610251;178610250	chr2:179474979;179474978;179474977
N2A	14524	43795;43796;43797	chr2:178610252;178610251;178610250	chr2:179474979;179474978;179474977
N2B	8027	24304;24305;24306	chr2:178610252;178610251;178610250	chr2:179474979;179474978;179474977
Novex-1	8152	24679;24680;24681	chr2:178610252;178610251;178610250	chr2:179474979;179474978;179474977
Novex-2	8219	24880;24881;24882	chr2:178610252;178610251;178610250	chr2:179474979;179474978;179474977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-12
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9637
• 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
R/K	rs1207362275	0.134	0.046	N	0.467	0.107	0.238096912614	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/K	rs1207362275	0.134	0.046	N	0.467	0.107	0.238096912614	gnomAD-4.0.0	6.84498E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99815E-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
R/A	0.9507	likely_pathogenic	0.8982	pathogenic	-0.013	Destabilizing	0.953	D	0.609	neutral	None	None	None	None	N
R/C	0.8245	likely_pathogenic	0.7156	pathogenic	-0.32	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
R/D	0.9828	likely_pathogenic	0.9627	pathogenic	-0.366	Destabilizing	0.986	D	0.623	neutral	None	None	None	None	N
R/E	0.9362	likely_pathogenic	0.873	pathogenic	-0.337	Destabilizing	0.91	D	0.618	neutral	None	None	None	None	N
R/F	0.9685	likely_pathogenic	0.9384	pathogenic	-0.36	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
R/G	0.9034	likely_pathogenic	0.8105	pathogenic	-0.125	Destabilizing	0.939	D	0.525	neutral	N	0.444055614	None	None	N
R/H	0.5934	likely_pathogenic	0.4306	ambiguous	-0.581	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
R/I	0.911	likely_pathogenic	0.8255	pathogenic	0.236	Stabilizing	0.991	D	0.676	prob.neutral	N	0.514766493	None	None	N
R/K	0.3264	likely_benign	0.2375	benign	-0.249	Destabilizing	0.046	N	0.467	neutral	N	0.425280639	None	None	N
R/L	0.8014	likely_pathogenic	0.6839	pathogenic	0.236	Stabilizing	0.953	D	0.525	neutral	None	None	None	None	N
R/M	0.868	likely_pathogenic	0.7689	pathogenic	-0.159	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
R/N	0.9634	likely_pathogenic	0.9294	pathogenic	-0.172	Destabilizing	0.986	D	0.587	neutral	None	None	None	None	N
R/P	0.97	likely_pathogenic	0.9225	pathogenic	0.169	Stabilizing	0.993	D	0.625	neutral	None	None	None	None	N
R/Q	0.5282	ambiguous	0.3729	ambiguous	-0.2	Destabilizing	0.986	D	0.587	neutral	None	None	None	None	N
R/S	0.9722	likely_pathogenic	0.941	pathogenic	-0.319	Destabilizing	0.939	D	0.581	neutral	N	0.463721597	None	None	N
R/T	0.9342	likely_pathogenic	0.8574	pathogenic	-0.199	Destabilizing	0.982	D	0.571	neutral	N	0.482846076	None	None	N
R/V	0.9249	likely_pathogenic	0.8608	pathogenic	0.169	Stabilizing	0.993	D	0.681	prob.neutral	None	None	None	None	N
R/W	0.8293	likely_pathogenic	0.6933	pathogenic	-0.569	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
R/Y	0.922	likely_pathogenic	0.8624	pathogenic	-0.18	Destabilizing	0.998	D	0.634	neutral	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.