TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21537	64834;64835;64836	chr2:178585135;178585134;178585133	chr2:179449862;179449861;179449860
N2AB	19896	59911;59912;59913	chr2:178585135;178585134;178585133	chr2:179449862;179449861;179449860
N2A	18969	57130;57131;57132	chr2:178585135;178585134;178585133	chr2:179449862;179449861;179449860
N2B	12472	37639;37640;37641	chr2:178585135;178585134;178585133	chr2:179449862;179449861;179449860
Novex-1	12597	38014;38015;38016	chr2:178585135;178585134;178585133	chr2:179449862;179449861;179449860
Novex-2	12664	38215;38216;38217	chr2:178585135;178585134;178585133	chr2:179449862;179449861;179449860
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-124
• Domain position: 69
• Structural Position: 154
• Q(SASA): 0.149
• 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
Y/H	None	None	1.0	D	0.788	0.818	0.713973972888	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-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
Y/A	0.9957	likely_pathogenic	0.9942	pathogenic	-1.732	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/C	0.9083	likely_pathogenic	0.8803	pathogenic	-1.27	Destabilizing	1.0	D	0.838	deleterious	D	0.637404035	None	None	N
Y/D	0.9966	likely_pathogenic	0.9953	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.637404035	None	None	N
Y/E	0.9988	likely_pathogenic	0.9983	pathogenic	-1.914	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/F	0.1416	likely_benign	0.1404	benign	-0.369	Destabilizing	0.999	D	0.707	prob.neutral	D	0.581554153	None	None	N
Y/G	0.9919	likely_pathogenic	0.9896	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/H	0.9381	likely_pathogenic	0.9182	pathogenic	-1.598	Destabilizing	1.0	D	0.788	deleterious	D	0.63720223	None	None	N
Y/I	0.9174	likely_pathogenic	0.8981	pathogenic	-0.259	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9973	pathogenic	-1.426	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/L	0.8594	likely_pathogenic	0.8399	pathogenic	-0.259	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
Y/M	0.9792	likely_pathogenic	0.9741	pathogenic	-0.44	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
Y/N	0.9862	likely_pathogenic	0.9807	pathogenic	-2.306	Highly Destabilizing	1.0	D	0.864	deleterious	D	0.637404035	None	None	N
Y/P	0.9979	likely_pathogenic	0.9974	pathogenic	-0.762	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/Q	0.9973	likely_pathogenic	0.996	pathogenic	-1.813	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/R	0.9909	likely_pathogenic	0.9874	pathogenic	-1.831	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/S	0.9864	likely_pathogenic	0.9821	pathogenic	-2.671	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.637404035	None	None	N
Y/T	0.9942	likely_pathogenic	0.9919	pathogenic	-2.268	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/V	0.9025	likely_pathogenic	0.8818	pathogenic	-0.762	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
Y/W	0.6986	likely_pathogenic	0.6921	pathogenic	0.221	Stabilizing	1.0	D	0.779	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.