TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21935	66028;66029;66030	chr2:178583000;178582999;178582998	chr2:179447727;179447726;179447725
N2AB	20294	61105;61106;61107	chr2:178583000;178582999;178582998	chr2:179447727;179447726;179447725
N2A	19367	58324;58325;58326	chr2:178583000;178582999;178582998	chr2:179447727;179447726;179447725
N2B	12870	38833;38834;38835	chr2:178583000;178582999;178582998	chr2:179447727;179447726;179447725
Novex-1	12995	39208;39209;39210	chr2:178583000;178582999;178582998	chr2:179447727;179447726;179447725
Novex-2	13062	39409;39410;39411	chr2:178583000;178582999;178582998	chr2:179447727;179447726;179447725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-125
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.1751
• 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
T/A	rs1340276785	-1.356	0.863	N	0.586	0.266	0.180583059064	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.08E-06	0
T/A	rs1340276785	-1.356	0.863	N	0.586	0.266	0.180583059064	gnomAD-4.0.0	1.65038E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96648E-06	0	0
T/I	rs571121441	0.028	0.885	N	0.578	0.246	0.342865806769	gnomAD-2.1.1	8.3E-06	None	None	None	None	N	None	0	6.1E-05	None	0	0	None	0	None	0	0	0
T/I	rs571121441	0.028	0.885	N	0.578	0.246	0.342865806769	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96644E-04	0	0	0	None	0	0	0	0	0
T/I	rs571121441	0.028	0.885	N	0.578	0.246	0.342865806769	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
T/I	rs571121441	0.028	0.885	N	0.578	0.246	0.342865806769	gnomAD-4.0.0	1.13241E-05	None	None	None	None	N	None	0	2.23675E-04	None	0	0	None	0	0	2.57269E-06	2.31766E-05	0
T/N	rs571121441	None	0.997	N	0.593	0.311	0.353974658523	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
T/N	rs571121441	None	0.997	N	0.593	0.311	0.353974658523	gnomAD-4.0.0	1.25833E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.5749E-05	0	8.57556E-07	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
T/A	0.1186	likely_benign	0.1068	benign	-1.26	Destabilizing	0.863	D	0.586	neutral	N	0.464116039	None	None	N
T/C	0.3669	ambiguous	0.3098	benign	-1.204	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
T/D	0.6277	likely_pathogenic	0.5723	pathogenic	-1.633	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
T/E	0.3767	ambiguous	0.3327	benign	-1.477	Destabilizing	0.993	D	0.655	neutral	None	None	None	None	N
T/F	0.3348	likely_benign	0.2844	benign	-1.271	Destabilizing	0.986	D	0.739	prob.delet.	None	None	None	None	N
T/G	0.4031	ambiguous	0.3777	ambiguous	-1.599	Destabilizing	0.993	D	0.671	neutral	None	None	None	None	N
T/H	0.3091	likely_benign	0.2639	benign	-1.788	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
T/I	0.1423	likely_benign	0.1162	benign	-0.389	Destabilizing	0.885	D	0.578	neutral	N	0.486534168	None	None	N
T/K	0.3173	likely_benign	0.2722	benign	-0.557	Destabilizing	0.993	D	0.656	neutral	None	None	None	None	N
T/L	0.136	likely_benign	0.1143	benign	-0.389	Destabilizing	0.591	D	0.595	neutral	None	None	None	None	N
T/M	0.0942	likely_benign	0.0851	benign	-0.337	Destabilizing	0.807	D	0.546	neutral	None	None	None	None	N
T/N	0.2243	likely_benign	0.2046	benign	-1.163	Destabilizing	0.997	D	0.593	neutral	N	0.472536284	None	None	N
T/P	0.9043	likely_pathogenic	0.8947	pathogenic	-0.65	Destabilizing	0.997	D	0.686	prob.neutral	N	0.50488368	None	None	N
T/Q	0.2639	likely_benign	0.2306	benign	-1.125	Destabilizing	0.993	D	0.701	prob.neutral	None	None	None	None	N
T/R	0.2583	likely_benign	0.2088	benign	-0.62	Destabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	N
T/S	0.1442	likely_benign	0.1356	benign	-1.381	Destabilizing	0.969	D	0.566	neutral	N	0.488803682	None	None	N
T/V	0.1127	likely_benign	0.0983	benign	-0.65	Destabilizing	0.214	N	0.513	neutral	None	None	None	None	N
T/W	0.7234	likely_pathogenic	0.6689	pathogenic	-1.336	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
T/Y	0.387	ambiguous	0.3425	ambiguous	-0.956	Destabilizing	0.993	D	0.759	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.