TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17069	51430;51431;51432	chr2:178610321;178610320;178610319	chr2:179475048;179475047;179475046
N2AB	15428	46507;46508;46509	chr2:178610321;178610320;178610319	chr2:179475048;179475047;179475046
N2A	14501	43726;43727;43728	chr2:178610321;178610320;178610319	chr2:179475048;179475047;179475046
N2B	8004	24235;24236;24237	chr2:178610321;178610320;178610319	chr2:179475048;179475047;179475046
Novex-1	8129	24610;24611;24612	chr2:178610321;178610320;178610319	chr2:179475048;179475047;179475046
Novex-2	8196	24811;24812;24813	chr2:178610321;178610320;178610319	chr2:179475048;179475047;179475046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-12
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4166
• 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/G	None	None	0.994	N	0.672	0.511	0.399596177874	gnomAD-4.0.0	1.59323E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88253E-05	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
E/A	0.2134	likely_benign	0.1905	benign	-0.866	Destabilizing	0.994	D	0.643	neutral	N	0.485165153	None	None	N
E/C	0.8311	likely_pathogenic	0.8712	pathogenic	-0.485	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.1221	likely_benign	0.1229	benign	-1.01	Destabilizing	0.104	N	0.177	neutral	N	0.473648743	None	None	N
E/F	0.7784	likely_pathogenic	0.8226	pathogenic	-0.41	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/G	0.2782	likely_benign	0.2628	benign	-1.199	Destabilizing	0.994	D	0.672	neutral	N	0.484590882	None	None	N
E/H	0.6155	likely_pathogenic	0.632	pathogenic	-0.642	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
E/I	0.3811	ambiguous	0.3853	ambiguous	0.033	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/K	0.322	likely_benign	0.326	benign	-0.697	Destabilizing	0.994	D	0.501	neutral	N	0.458879787	None	None	N
E/L	0.3926	ambiguous	0.3844	ambiguous	0.033	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/M	0.4577	ambiguous	0.4552	ambiguous	0.427	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/N	0.2528	likely_benign	0.2705	benign	-1.044	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
E/P	0.9695	likely_pathogenic	0.9444	pathogenic	-0.245	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Q	0.1892	likely_benign	0.1776	benign	-0.931	Destabilizing	0.998	D	0.612	neutral	N	0.482607243	None	None	N
E/R	0.5186	ambiguous	0.5282	ambiguous	-0.384	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
E/S	0.2241	likely_benign	0.2214	benign	-1.334	Destabilizing	0.992	D	0.526	neutral	None	None	None	None	N
E/T	0.2482	likely_benign	0.2421	benign	-1.068	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/V	0.253	likely_benign	0.2404	benign	-0.245	Destabilizing	0.999	D	0.768	deleterious	N	0.477775341	None	None	N
E/W	0.9438	likely_pathogenic	0.9548	pathogenic	-0.186	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Y	0.6811	likely_pathogenic	0.7334	pathogenic	-0.187	Destabilizing	1.0	D	0.783	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.