TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18206	54841;54842;54843	chr2:178604071;178604070;178604069	chr2:179468798;179468797;179468796
N2AB	16565	49918;49919;49920	chr2:178604071;178604070;178604069	chr2:179468798;179468797;179468796
N2A	15638	47137;47138;47139	chr2:178604071;178604070;178604069	chr2:179468798;179468797;179468796
N2B	9141	27646;27647;27648	chr2:178604071;178604070;178604069	chr2:179468798;179468797;179468796
Novex-1	9266	28021;28022;28023	chr2:178604071;178604070;178604069	chr2:179468798;179468797;179468796
Novex-2	9333	28222;28223;28224	chr2:178604071;178604070;178604069	chr2:179468798;179468797;179468796
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: Fn3-20
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.2035
• 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/T	None	None	0.003	N	0.309	0.371	0.312001716656	gnomAD-4.0.0	1.59315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02792E-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
R/A	0.8397	likely_pathogenic	0.7385	pathogenic	-2.045	Highly Destabilizing	0.218	N	0.551	neutral	None	None	None	None	N
R/C	0.3508	ambiguous	0.3039	benign	-1.941	Destabilizing	0.973	D	0.741	deleterious	None	None	None	None	N
R/D	0.9797	likely_pathogenic	0.9737	pathogenic	-1.086	Destabilizing	0.826	D	0.676	prob.neutral	None	None	None	None	N
R/E	0.8086	likely_pathogenic	0.7604	pathogenic	-0.87	Destabilizing	0.404	N	0.497	neutral	None	None	None	None	N
R/F	0.8506	likely_pathogenic	0.7701	pathogenic	-1.275	Destabilizing	0.906	D	0.746	deleterious	None	None	None	None	N
R/G	0.7588	likely_pathogenic	0.6646	pathogenic	-2.377	Highly Destabilizing	0.505	D	0.613	neutral	N	0.501237873	None	None	N
R/H	0.3053	likely_benign	0.2753	benign	-2.254	Highly Destabilizing	0.967	D	0.548	neutral	None	None	None	None	N
R/I	0.7689	likely_pathogenic	0.6275	pathogenic	-1.077	Destabilizing	0.642	D	0.748	deleterious	N	0.509378175	None	None	N
R/K	0.1595	likely_benign	0.1067	benign	-1.363	Destabilizing	0.001	N	0.149	neutral	N	0.488446683	None	None	N
R/L	0.6017	likely_pathogenic	0.4199	ambiguous	-1.077	Destabilizing	0.404	N	0.592	neutral	None	None	None	None	N
R/M	0.5661	likely_pathogenic	0.4263	ambiguous	-1.58	Destabilizing	0.973	D	0.646	neutral	None	None	None	None	N
R/N	0.9374	likely_pathogenic	0.9136	pathogenic	-1.378	Destabilizing	0.575	D	0.533	neutral	None	None	None	None	N
R/P	0.9953	likely_pathogenic	0.9914	pathogenic	-1.39	Destabilizing	0.906	D	0.726	prob.delet.	None	None	None	None	N
R/Q	0.1895	likely_benign	0.1711	benign	-1.22	Destabilizing	0.826	D	0.569	neutral	None	None	None	None	N
R/S	0.9199	likely_pathogenic	0.8796	pathogenic	-2.239	Highly Destabilizing	0.338	N	0.541	neutral	N	0.518692232	None	None	N
R/T	0.8367	likely_pathogenic	0.71	pathogenic	-1.815	Destabilizing	0.003	N	0.309	neutral	N	0.49776838	None	None	N
R/V	0.7884	likely_pathogenic	0.6635	pathogenic	-1.39	Destabilizing	0.704	D	0.677	prob.neutral	None	None	None	None	N
R/W	0.527	ambiguous	0.4688	ambiguous	-0.826	Destabilizing	0.991	D	0.744	deleterious	None	None	None	None	N
R/Y	0.7101	likely_pathogenic	0.6667	pathogenic	-0.684	Destabilizing	0.906	D	0.729	prob.delet.	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.