TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21868	65827;65828;65829	chr2:178583201;178583200;178583199	chr2:179447928;179447927;179447926
N2AB	20227	60904;60905;60906	chr2:178583201;178583200;178583199	chr2:179447928;179447927;179447926
N2A	19300	58123;58124;58125	chr2:178583201;178583200;178583199	chr2:179447928;179447927;179447926
N2B	12803	38632;38633;38634	chr2:178583201;178583200;178583199	chr2:179447928;179447927;179447926
Novex-1	12928	39007;39008;39009	chr2:178583201;178583200;178583199	chr2:179447928;179447927;179447926
Novex-2	12995	39208;39209;39210	chr2:178583201;178583200;178583199	chr2:179447928;179447927;179447926
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-125
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.4119
• 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/V	None	None	0.055	N	0.269	0.066	0.352910780287	gnomAD-4.0.0	1.60556E-06	None	None	None	None	N	None	0	2.29811E-05	None	0	0	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	0.4941	ambiguous	0.4453	ambiguous	-0.759	Destabilizing	0.864	D	0.383	neutral	None	None	None	None	N
A/D	0.1736	likely_benign	0.1547	benign	-0.277	Destabilizing	None	N	0.287	neutral	N	0.439546376	None	None	N
A/E	0.1175	likely_benign	0.1139	benign	-0.42	Destabilizing	None	N	0.19	neutral	None	None	None	None	N
A/F	0.392	ambiguous	0.34	ambiguous	-0.786	Destabilizing	0.628	D	0.473	neutral	None	None	None	None	N
A/G	0.1332	likely_benign	0.1246	benign	-0.253	Destabilizing	None	N	0.125	neutral	N	0.470216	None	None	N
A/H	0.3333	likely_benign	0.3028	benign	-0.293	Destabilizing	0.356	N	0.466	neutral	None	None	None	None	N
A/I	0.2515	likely_benign	0.2237	benign	-0.239	Destabilizing	0.136	N	0.486	neutral	None	None	None	None	N
A/K	0.2897	likely_benign	0.2588	benign	-0.554	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
A/L	0.1803	likely_benign	0.1635	benign	-0.239	Destabilizing	0.031	N	0.39	neutral	None	None	None	None	N
A/M	0.2248	likely_benign	0.2073	benign	-0.378	Destabilizing	0.628	D	0.396	neutral	None	None	None	None	N
A/N	0.1658	likely_benign	0.151	benign	-0.238	Destabilizing	None	N	0.281	neutral	None	None	None	None	N
A/P	0.1652	likely_benign	0.1526	benign	-0.191	Destabilizing	0.106	N	0.405	neutral	N	0.43277512	None	None	N
A/Q	0.1853	likely_benign	0.1743	benign	-0.478	Destabilizing	0.001	N	0.233	neutral	None	None	None	None	N
A/R	0.331	likely_benign	0.297	benign	-0.143	Destabilizing	0.038	N	0.395	neutral	None	None	None	None	N
A/S	0.082	likely_benign	0.0777	benign	-0.468	Destabilizing	None	N	0.087	neutral	N	0.416378728	None	None	N
A/T	0.0742	likely_benign	0.0709	benign	-0.523	Destabilizing	0.012	N	0.237	neutral	N	0.428425306	None	None	N
A/V	0.1283	likely_benign	0.1202	benign	-0.191	Destabilizing	0.055	N	0.269	neutral	N	0.458652212	None	None	N
A/W	0.7017	likely_pathogenic	0.6633	pathogenic	-0.942	Destabilizing	0.864	D	0.492	neutral	None	None	None	None	N
A/Y	0.4459	ambiguous	0.4054	ambiguous	-0.582	Destabilizing	0.628	D	0.483	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.