TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28221	84886;84887;84888	chr2:178561471;178561470;178561469	chr2:179426198;179426197;179426196
N2AB	26580	79963;79964;79965	chr2:178561471;178561470;178561469	chr2:179426198;179426197;179426196
N2A	25653	77182;77183;77184	chr2:178561471;178561470;178561469	chr2:179426198;179426197;179426196
N2B	19156	57691;57692;57693	chr2:178561471;178561470;178561469	chr2:179426198;179426197;179426196
Novex-1	19281	58066;58067;58068	chr2:178561471;178561470;178561469	chr2:179426198;179426197;179426196
Novex-2	19348	58267;58268;58269	chr2:178561471;178561470;178561469	chr2:179426198;179426197;179426196
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: Fn3-93
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.391
• 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	0.892	N	0.438	0.44	0.42886291518	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs1309034017	0.146	0.805	N	0.521	0.308	0.346315397577	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs1309034017	0.146	0.805	N	0.521	0.308	0.346315397577	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1309034017	0.146	0.805	N	0.521	0.308	0.346315397577	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	2.41196E-05	0	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
E/A	0.3075	likely_benign	0.3585	ambiguous	-0.576	Destabilizing	0.892	D	0.421	neutral	N	0.480786079	None	None	N
E/C	0.956	likely_pathogenic	0.9659	pathogenic	-0.069	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
E/D	0.3414	ambiguous	0.4079	ambiguous	-0.59	Destabilizing	0.892	D	0.505	neutral	N	0.503426692	None	None	N
E/F	0.9649	likely_pathogenic	0.9728	pathogenic	-0.494	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
E/G	0.4859	ambiguous	0.5414	ambiguous	-0.806	Destabilizing	0.892	D	0.438	neutral	N	0.500717667	None	None	N
E/H	0.8628	likely_pathogenic	0.8915	pathogenic	-0.521	Destabilizing	0.997	D	0.453	neutral	None	None	None	None	N
E/I	0.7525	likely_pathogenic	0.7977	pathogenic	0.005	Stabilizing	0.987	D	0.601	neutral	None	None	None	None	N
E/K	0.4088	ambiguous	0.4751	ambiguous	0.068	Stabilizing	0.805	D	0.521	neutral	N	0.491056429	None	None	N
E/L	0.8391	likely_pathogenic	0.8812	pathogenic	0.005	Stabilizing	0.975	D	0.529	neutral	None	None	None	None	N
E/M	0.81	likely_pathogenic	0.8508	pathogenic	0.284	Stabilizing	0.999	D	0.507	neutral	None	None	None	None	N
E/N	0.6625	likely_pathogenic	0.7174	pathogenic	-0.201	Destabilizing	0.987	D	0.484	neutral	None	None	None	None	N
E/P	0.675	likely_pathogenic	0.7323	pathogenic	-0.168	Destabilizing	0.033	N	0.266	neutral	None	None	None	None	N
E/Q	0.3479	ambiguous	0.3893	ambiguous	-0.178	Destabilizing	0.426	N	0.264	neutral	N	0.516422718	None	None	N
E/R	0.5948	likely_pathogenic	0.6538	pathogenic	0.218	Stabilizing	0.975	D	0.483	neutral	None	None	None	None	N
E/S	0.4588	ambiguous	0.5046	ambiguous	-0.391	Destabilizing	0.916	D	0.5	neutral	None	None	None	None	N
E/T	0.5409	ambiguous	0.6004	pathogenic	-0.21	Destabilizing	0.975	D	0.366	neutral	None	None	None	None	N
E/V	0.542	ambiguous	0.6019	pathogenic	-0.168	Destabilizing	0.983	D	0.457	neutral	N	0.507212127	None	None	N
E/W	0.9909	likely_pathogenic	0.9931	pathogenic	-0.338	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
E/Y	0.94	likely_pathogenic	0.9547	pathogenic	-0.254	Destabilizing	0.996	D	0.53	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.