TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32368	97327;97328;97329	chr2:178542752;178542751;178542750	chr2:179407479;179407478;179407477
N2AB	30727	92404;92405;92406	chr2:178542752;178542751;178542750	chr2:179407479;179407478;179407477
N2A	29800	89623;89624;89625	chr2:178542752;178542751;178542750	chr2:179407479;179407478;179407477
N2B	23303	70132;70133;70134	chr2:178542752;178542751;178542750	chr2:179407479;179407478;179407477
Novex-1	23428	70507;70508;70509	chr2:178542752;178542751;178542750	chr2:179407479;179407478;179407477
Novex-2	23495	70708;70709;70710	chr2:178542752;178542751;178542750	chr2:179407479;179407478;179407477
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-154
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.4833
• 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/D	None	None	0.104	N	0.231	0.017	0.0846915920261	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-06	0	0
E/K	rs1695208937	None	0.994	N	0.523	0.339	0.233785782151	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	rs1695208937	None	0.994	N	0.523	0.339	0.233785782151	gnomAD-4.0.0	6.57402E-06	None	None	None	None	N	None	2.41383E-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	0.4162	ambiguous	0.3753	ambiguous	-0.38	Destabilizing	0.994	D	0.545	neutral	N	0.435371842	None	None	N
E/C	0.9576	likely_pathogenic	0.9475	pathogenic	0.114	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/D	0.1222	likely_benign	0.116	benign	-0.33	Destabilizing	0.104	N	0.231	neutral	N	0.383286796	None	None	N
E/F	0.9477	likely_pathogenic	0.9347	pathogenic	-0.365	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/G	0.3432	ambiguous	0.3081	benign	-0.573	Destabilizing	0.994	D	0.501	neutral	N	0.439700226	None	None	N
E/H	0.7551	likely_pathogenic	0.7157	pathogenic	-0.24	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	N
E/I	0.8488	likely_pathogenic	0.8108	pathogenic	0.093	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/K	0.4914	ambiguous	0.444	ambiguous	0.422	Stabilizing	0.994	D	0.523	neutral	N	0.432464823	None	None	N
E/L	0.834	likely_pathogenic	0.7929	pathogenic	0.093	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/M	0.8316	likely_pathogenic	0.8033	pathogenic	0.294	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	N
E/N	0.3639	ambiguous	0.3452	ambiguous	0.138	Stabilizing	0.998	D	0.55	neutral	None	None	None	None	N
E/P	0.9206	likely_pathogenic	0.9098	pathogenic	-0.044	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
E/Q	0.3217	likely_benign	0.2926	benign	0.16	Stabilizing	0.998	D	0.546	neutral	N	0.451437372	None	None	N
E/R	0.6588	likely_pathogenic	0.6221	pathogenic	0.529	Stabilizing	0.999	D	0.574	neutral	None	None	None	None	N
E/S	0.4067	ambiguous	0.3765	ambiguous	-0.025	Destabilizing	0.992	D	0.525	neutral	None	None	None	None	N
E/T	0.5501	ambiguous	0.5096	ambiguous	0.135	Stabilizing	0.999	D	0.545	neutral	None	None	None	None	N
E/V	0.6661	likely_pathogenic	0.6161	pathogenic	-0.044	Destabilizing	0.999	D	0.617	neutral	N	0.465868107	None	None	N
E/W	0.9789	likely_pathogenic	0.9732	pathogenic	-0.239	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.8661	likely_pathogenic	0.8363	pathogenic	-0.12	Destabilizing	1.0	D	0.627	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.