TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5206	15841;15842;15843	chr2:178733773;178733772;178733771	chr2:179598500;179598499;179598498
N2AB	4889	14890;14891;14892	chr2:178733773;178733772;178733771	chr2:179598500;179598499;179598498
N2A	3962	12109;12110;12111	chr2:178733773;178733772;178733771	chr2:179598500;179598499;179598498
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-35
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.5377
• 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
E/K	None	None	0.003	N	0.287	0.159	0.297031009988	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
E/A	0.1268	likely_benign	0.1332	benign	-0.309	Destabilizing	0.338	N	0.444	neutral	D	0.543018393	None	None	N
E/C	0.747	likely_pathogenic	0.7921	pathogenic	-0.229	Destabilizing	0.991	D	0.639	neutral	None	None	None	None	N
E/D	0.083	likely_benign	0.0932	benign	-0.333	Destabilizing	0.001	N	0.234	neutral	D	0.538882695	None	None	N
E/F	0.6128	likely_pathogenic	0.6801	pathogenic	-0.133	Destabilizing	0.967	D	0.597	neutral	None	None	None	None	N
E/G	0.1516	likely_benign	0.163	benign	-0.499	Destabilizing	0.505	D	0.427	neutral	D	0.548465147	None	None	N
E/H	0.3007	likely_benign	0.3256	benign	0.254	Stabilizing	0.973	D	0.389	neutral	None	None	None	None	N
E/I	0.2668	likely_benign	0.3007	benign	0.153	Stabilizing	0.906	D	0.603	neutral	None	None	None	None	N
E/K	0.118	likely_benign	0.1121	benign	0.247	Stabilizing	0.003	N	0.287	neutral	N	0.501069412	None	None	N
E/L	0.3003	likely_benign	0.3369	benign	0.153	Stabilizing	0.826	D	0.569	neutral	None	None	None	None	N
E/M	0.3378	likely_benign	0.3682	ambiguous	0.073	Stabilizing	0.991	D	0.553	neutral	None	None	None	None	N
E/N	0.1465	likely_benign	0.1623	benign	-0.112	Destabilizing	0.404	N	0.366	neutral	None	None	None	None	N
E/P	0.7627	likely_pathogenic	0.7707	pathogenic	0.019	Stabilizing	0.906	D	0.444	neutral	None	None	None	None	N
E/Q	0.1189	likely_benign	0.1171	benign	-0.064	Destabilizing	0.338	N	0.373	neutral	N	0.50672401	None	None	N
E/R	0.2102	likely_benign	0.2018	benign	0.537	Stabilizing	0.704	D	0.355	neutral	None	None	None	None	N
E/S	0.1569	likely_benign	0.164	benign	-0.266	Destabilizing	0.404	N	0.403	neutral	None	None	None	None	N
E/T	0.1592	likely_benign	0.1687	benign	-0.108	Destabilizing	0.826	D	0.366	neutral	None	None	None	None	N
E/V	0.1554	likely_benign	0.173	benign	0.019	Stabilizing	0.782	D	0.499	neutral	N	0.511970139	None	None	N
E/W	0.793	likely_pathogenic	0.8326	pathogenic	0.015	Stabilizing	0.991	D	0.661	neutral	None	None	None	None	N
E/Y	0.4361	ambiguous	0.496	ambiguous	0.104	Stabilizing	0.967	D	0.542	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.