TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21947	66064;66065;66066	chr2:178582964;178582963;178582962	chr2:179447691;179447690;179447689
N2AB	20306	61141;61142;61143	chr2:178582964;178582963;178582962	chr2:179447691;179447690;179447689
N2A	19379	58360;58361;58362	chr2:178582964;178582963;178582962	chr2:179447691;179447690;179447689
N2B	12882	38869;38870;38871	chr2:178582964;178582963;178582962	chr2:179447691;179447690;179447689
Novex-1	13007	39244;39245;39246	chr2:178582964;178582963;178582962	chr2:179447691;179447690;179447689
Novex-2	13074	39445;39446;39447	chr2:178582964;178582963;178582962	chr2:179447691;179447690;179447689
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-125
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.1251
• 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
A/P	rs1434065340	-0.845	0.983	D	0.773	0.69	0.553872852973	gnomAD-4.0.0	1.82037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.37701E-05
A/V	rs2154178631	None	0.892	N	0.652	0.365	0.473695954338	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94175E-04	None	0	0	0	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
A/C	0.556	ambiguous	0.4773	ambiguous	-0.791	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
A/D	0.6962	likely_pathogenic	0.6498	pathogenic	-0.218	Destabilizing	0.935	D	0.76	deleterious	N	0.499547985	None	None	N
A/E	0.5689	likely_pathogenic	0.5092	ambiguous	-0.351	Destabilizing	0.253	N	0.458	neutral	None	None	None	None	N
A/F	0.6065	likely_pathogenic	0.5692	pathogenic	-0.835	Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	N
A/G	0.2158	likely_benign	0.2017	benign	-0.404	Destabilizing	0.805	D	0.585	neutral	D	0.536582639	None	None	N
A/H	0.7784	likely_pathogenic	0.7134	pathogenic	-0.468	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
A/I	0.466	ambiguous	0.4074	ambiguous	-0.268	Destabilizing	0.987	D	0.775	deleterious	None	None	None	None	N
A/K	0.7944	likely_pathogenic	0.737	pathogenic	-0.596	Destabilizing	0.916	D	0.722	prob.delet.	None	None	None	None	N
A/L	0.4133	ambiguous	0.3694	ambiguous	-0.268	Destabilizing	0.916	D	0.706	prob.neutral	None	None	None	None	N
A/M	0.3798	ambiguous	0.3256	benign	-0.335	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
A/N	0.6119	likely_pathogenic	0.5598	ambiguous	-0.294	Destabilizing	0.975	D	0.788	deleterious	None	None	None	None	N
A/P	0.992	likely_pathogenic	0.9903	pathogenic	-0.247	Destabilizing	0.983	D	0.773	deleterious	D	0.534795443	None	None	N
A/Q	0.586	likely_pathogenic	0.5064	ambiguous	-0.528	Destabilizing	0.975	D	0.774	deleterious	None	None	None	None	N
A/R	0.7621	likely_pathogenic	0.6943	pathogenic	-0.203	Destabilizing	0.975	D	0.773	deleterious	None	None	None	None	N
A/S	0.1425	likely_benign	0.1355	benign	-0.569	Destabilizing	0.099	N	0.405	neutral	N	0.496522741	None	None	N
A/T	0.1322	likely_benign	0.1201	benign	-0.608	Destabilizing	0.805	D	0.639	neutral	N	0.508355888	None	None	N
A/V	0.2136	likely_benign	0.1852	benign	-0.247	Destabilizing	0.892	D	0.652	neutral	N	0.516148652	None	None	N
A/W	0.948	likely_pathogenic	0.926	pathogenic	-0.999	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
A/Y	0.7724	likely_pathogenic	0.7191	pathogenic	-0.63	Destabilizing	0.996	D	0.819	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.