TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29589	88990;88991;88992	chr2:178554582;178554581;178554580	chr2:179419309;179419308;179419307
N2AB	27948	84067;84068;84069	chr2:178554582;178554581;178554580	chr2:179419309;179419308;179419307
N2A	27021	81286;81287;81288	chr2:178554582;178554581;178554580	chr2:179419309;179419308;179419307
N2B	20524	61795;61796;61797	chr2:178554582;178554581;178554580	chr2:179419309;179419308;179419307
Novex-1	20649	62170;62171;62172	chr2:178554582;178554581;178554580	chr2:179419309;179419308;179419307
Novex-2	20716	62371;62372;62373	chr2:178554582;178554581;178554580	chr2:179419309;179419308;179419307
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: Fn3-103
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.719
• Predicted PPI site: I

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	rs773486662	0.483	0.852	N	0.251	0.251	0.241664281697	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs773486662	0.483	0.852	N	0.251	0.251	0.241664281697	gnomAD-4.0.0	2.0525E-06	None	None	None	None	I	None	5.97443E-05	0	None	0	2.52016E-05	None	0	0	0	0	0
E/Q	rs773486662	0.044	0.31	N	0.147	0.151	0.247872288689	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs773486662	0.044	0.31	N	0.147	0.151	0.247872288689	gnomAD-4.0.0	6.84166E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-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	0.1445	likely_benign	0.156	benign	-0.679	Destabilizing	0.826	D	0.3	neutral	N	0.417258589	None	None	I
E/C	0.8385	likely_pathogenic	0.8342	pathogenic	-0.522	Destabilizing	0.999	D	0.268	neutral	None	None	None	None	I
E/D	0.1346	likely_benign	0.1381	benign	-0.709	Destabilizing	0.92	D	0.261	neutral	N	0.430841174	None	None	I
E/F	0.8143	likely_pathogenic	0.8324	pathogenic	-0.157	Destabilizing	0.982	D	0.293	neutral	None	None	None	None	I
E/G	0.1471	likely_benign	0.156	benign	-0.967	Destabilizing	0.959	D	0.333	neutral	N	0.417143945	None	None	I
E/H	0.4391	ambiguous	0.454	ambiguous	-0.038	Destabilizing	0.991	D	0.333	neutral	None	None	None	None	I
E/I	0.4193	ambiguous	0.4372	ambiguous	0.088	Stabilizing	0.884	D	0.314	neutral	None	None	None	None	I
E/K	0.1205	likely_benign	0.132	benign	-0.408	Destabilizing	0.852	D	0.251	neutral	N	0.391112137	None	None	I
E/L	0.3778	ambiguous	0.3953	ambiguous	0.088	Stabilizing	0.046	N	0.241	neutral	None	None	None	None	I
E/M	0.4777	ambiguous	0.4942	ambiguous	0.175	Stabilizing	0.982	D	0.276	neutral	None	None	None	None	I
E/N	0.2451	likely_benign	0.258	benign	-0.816	Destabilizing	0.991	D	0.295	neutral	None	None	None	None	I
E/P	0.3018	likely_benign	0.3173	benign	-0.147	Destabilizing	0.997	D	0.325	neutral	None	None	None	None	I
E/Q	0.1221	likely_benign	0.1308	benign	-0.717	Destabilizing	0.31	N	0.147	neutral	N	0.381087145	None	None	I
E/R	0.219	likely_benign	0.2288	benign	0.023	Stabilizing	0.939	D	0.303	neutral	None	None	None	None	I
E/S	0.1858	likely_benign	0.1923	benign	-1.05	Destabilizing	0.939	D	0.23	neutral	None	None	None	None	I
E/T	0.1928	likely_benign	0.205	benign	-0.816	Destabilizing	0.939	D	0.303	neutral	None	None	None	None	I
E/V	0.2313	likely_benign	0.2442	benign	-0.147	Destabilizing	0.061	N	0.153	neutral	N	0.430187814	None	None	I
E/W	0.8935	likely_pathogenic	0.8994	pathogenic	0.093	Stabilizing	0.999	D	0.298	neutral	None	None	None	None	I
E/Y	0.685	likely_pathogenic	0.6973	pathogenic	0.08	Stabilizing	0.997	D	0.297	neutral	None	None	None	None	I

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.