TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9504	28735;28736;28737	chr2:178709809;178709808;178709807	chr2:179574536;179574535;179574534
N2AB	9187	27784;27785;27786	chr2:178709809;178709808;178709807	chr2:179574536;179574535;179574534
N2A	8260	25003;25004;25005	chr2:178709809;178709808;178709807	chr2:179574536;179574535;179574534
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-81
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.6163
• 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	0.998	None	0.598	0.46	0.544082543865	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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	0.2773	likely_benign	0.2093	benign	-0.457	Destabilizing	0.989	D	0.562	neutral	None	None	None	None	N
E/C	0.9551	likely_pathogenic	0.9291	pathogenic	-0.161	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/D	0.3809	ambiguous	0.3021	benign	-0.514	Destabilizing	0.998	D	0.479	neutral	None	None	None	None	N
E/F	0.9066	likely_pathogenic	0.8437	pathogenic	-0.204	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
E/G	0.4076	ambiguous	0.2829	benign	-0.686	Destabilizing	0.998	D	0.598	neutral	None	None	None	None	N
E/H	0.7987	likely_pathogenic	0.7019	pathogenic	-0.001	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/I	0.5252	ambiguous	0.4094	ambiguous	0.123	Stabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	N
E/K	0.3474	ambiguous	0.2275	benign	0.221	Stabilizing	0.994	D	0.547	neutral	None	None	None	None	N
E/L	0.6105	likely_pathogenic	0.4818	ambiguous	0.123	Stabilizing	0.983	D	0.583	neutral	None	None	None	None	N
E/M	0.6247	likely_pathogenic	0.5204	ambiguous	0.2	Stabilizing	0.96	D	0.436	neutral	None	None	None	None	N
E/N	0.589	likely_pathogenic	0.4754	ambiguous	-0.214	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/P	0.9222	likely_pathogenic	0.8702	pathogenic	-0.05	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/Q	0.2538	likely_benign	0.1995	benign	-0.165	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	N
E/R	0.5219	ambiguous	0.3776	ambiguous	0.48	Stabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
E/S	0.3876	ambiguous	0.3015	benign	-0.365	Destabilizing	0.996	D	0.584	neutral	None	None	None	None	N
E/T	0.3331	likely_benign	0.2535	benign	-0.177	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/V	0.2986	likely_benign	0.2209	benign	-0.05	Destabilizing	0.978	D	0.565	neutral	None	None	None	None	N
E/W	0.9695	likely_pathogenic	0.9401	pathogenic	-0.006	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/Y	0.8676	likely_pathogenic	0.7898	pathogenic	0.052	Stabilizing	1.0	D	0.691	prob.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.