TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7952	24079;24080;24081	chr2:178719638;178719637;178719636	chr2:179584365;179584364;179584363
N2AB	7635	23128;23129;23130	chr2:178719638;178719637;178719636	chr2:179584365;179584364;179584363
N2A	6708	20347;20348;20349	chr2:178719638;178719637;178719636	chr2:179584365;179584364;179584363
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-64
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2679
• 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/K	rs752227139	0.247	0.977	N	0.505	0.32	0.402899589544	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	6.54E-05	None	0	1.56E-05	0
E/K	rs752227139	0.247	0.977	N	0.505	0.32	0.402899589544	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	4.83E-05	6.55E-05	0	0	0	None	0	0	4.41E-05	0	4.77555E-04
E/K	rs752227139	0.247	0.977	N	0.505	0.32	0.402899589544	gnomAD-4.0.0	4.15235E-05	None	None	None	None	N	None	2.6718E-05	5.00183E-05	None	0	2.22856E-05	None	0	0	4.5773E-05	3.29417E-05	6.40471E-05

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	0.1236	likely_benign	0.1372	benign	-0.41	Destabilizing	0.939	D	0.493	neutral	N	0.487268539	None	None	N
E/C	0.7908	likely_pathogenic	0.8234	pathogenic	0.063	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/D	0.112	likely_benign	0.121	benign	-0.371	Destabilizing	0.02	N	0.153	neutral	N	0.479091773	None	None	N
E/F	0.6682	likely_pathogenic	0.7051	pathogenic	-0.321	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
E/G	0.1058	likely_benign	0.1199	benign	-0.632	Destabilizing	0.939	D	0.539	neutral	N	0.505643656	None	None	N
E/H	0.3532	ambiguous	0.3867	ambiguous	-0.247	Destabilizing	0.998	D	0.503	neutral	None	None	None	None	N
E/I	0.359	ambiguous	0.4004	ambiguous	0.144	Stabilizing	0.993	D	0.722	prob.delet.	None	None	None	None	N
E/K	0.0945	likely_benign	0.1085	benign	0.251	Stabilizing	0.977	D	0.505	neutral	N	0.463428888	None	None	N
E/L	0.3216	likely_benign	0.368	ambiguous	0.144	Stabilizing	0.993	D	0.681	prob.neutral	None	None	None	None	N
E/M	0.3852	ambiguous	0.421	ambiguous	0.38	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/N	0.1786	likely_benign	0.2055	benign	-0.035	Destabilizing	0.973	D	0.503	neutral	None	None	None	None	N
E/P	0.8105	likely_pathogenic	0.8451	pathogenic	-0.02	Destabilizing	0.993	D	0.591	neutral	None	None	None	None	N
E/Q	0.1101	likely_benign	0.1191	benign	0.012	Stabilizing	0.778	D	0.252	neutral	N	0.459735221	None	None	N
E/R	0.1656	likely_benign	0.182	benign	0.408	Stabilizing	0.986	D	0.524	neutral	None	None	None	None	N
E/S	0.1471	likely_benign	0.1633	benign	-0.223	Destabilizing	0.953	D	0.468	neutral	None	None	None	None	N
E/T	0.1761	likely_benign	0.1999	benign	-0.044	Destabilizing	0.986	D	0.532	neutral	None	None	None	None	N
E/V	0.1925	likely_benign	0.2121	benign	-0.02	Destabilizing	0.991	D	0.637	neutral	N	0.508683962	None	None	N
E/W	0.8484	likely_pathogenic	0.8738	pathogenic	-0.187	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
E/Y	0.5449	ambiguous	0.5866	pathogenic	-0.084	Destabilizing	0.998	D	0.685	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.