TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19146	57661;57662;57663	chr2:178597646;178597645;178597644	chr2:179462373;179462372;179462371
N2AB	17505	52738;52739;52740	chr2:178597646;178597645;178597644	chr2:179462373;179462372;179462371
N2A	16578	49957;49958;49959	chr2:178597646;178597645;178597644	chr2:179462373;179462372;179462371
N2B	10081	30466;30467;30468	chr2:178597646;178597645;178597644	chr2:179462373;179462372;179462371
Novex-1	10206	30841;30842;30843	chr2:178597646;178597645;178597644	chr2:179462373;179462372;179462371
Novex-2	10273	31042;31043;31044	chr2:178597646;178597645;178597644	chr2:179462373;179462372;179462371
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-117
• Domain position: 52
• Structural Position: 136
• Q(SASA): 0.1679
• 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
S/L	rs1427077002	0.074	0.959	N	0.733	0.355	0.78372721315	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
S/L	rs1427077002	0.074	0.959	N	0.733	0.355	0.78372721315	gnomAD-4.0.0	4.7771E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.76591E-05	0	0	1.43299E-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
S/A	0.1581	likely_benign	0.1669	benign	-1.025	Destabilizing	0.826	D	0.674	neutral	N	0.509777253	None	None	N
S/C	0.1289	likely_benign	0.1322	benign	-0.718	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
S/D	0.9566	likely_pathogenic	0.9623	pathogenic	-0.866	Destabilizing	0.884	D	0.725	prob.delet.	None	None	None	None	N
S/E	0.9741	likely_pathogenic	0.9745	pathogenic	-0.7	Destabilizing	0.939	D	0.72	prob.delet.	None	None	None	None	N
S/F	0.8223	likely_pathogenic	0.8593	pathogenic	-1.089	Destabilizing	0.997	D	0.739	prob.delet.	None	None	None	None	N
S/G	0.3735	ambiguous	0.4441	ambiguous	-1.389	Destabilizing	0.863	D	0.728	prob.delet.	None	None	None	None	N
S/H	0.8347	likely_pathogenic	0.846	pathogenic	-1.72	Destabilizing	0.991	D	0.732	prob.delet.	None	None	None	None	N
S/I	0.5947	likely_pathogenic	0.6265	pathogenic	-0.106	Destabilizing	0.997	D	0.763	deleterious	None	None	None	None	N
S/K	0.9924	likely_pathogenic	0.9924	pathogenic	-0.066	Destabilizing	0.17	N	0.471	neutral	None	None	None	None	N
S/L	0.4696	ambiguous	0.5202	ambiguous	-0.106	Destabilizing	0.959	D	0.733	prob.delet.	N	0.494468649	None	None	N
S/M	0.5777	likely_pathogenic	0.5981	pathogenic	-0.087	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
S/N	0.6035	likely_pathogenic	0.6234	pathogenic	-0.627	Destabilizing	0.079	N	0.389	neutral	None	None	None	None	N
S/P	0.9958	likely_pathogenic	0.997	pathogenic	-0.379	Destabilizing	0.996	D	0.773	deleterious	N	0.500509036	None	None	N
S/Q	0.9343	likely_pathogenic	0.9336	pathogenic	-0.485	Destabilizing	0.982	D	0.782	deleterious	None	None	None	None	N
S/R	0.9839	likely_pathogenic	0.9853	pathogenic	-0.411	Destabilizing	0.884	D	0.732	prob.delet.	None	None	None	None	N
S/T	0.1087	likely_benign	0.1134	benign	-0.455	Destabilizing	0.826	D	0.697	prob.neutral	N	0.452923892	None	None	N
S/V	0.4353	ambiguous	0.4679	ambiguous	-0.379	Destabilizing	0.991	D	0.765	deleterious	None	None	None	None	N
S/W	0.9075	likely_pathogenic	0.9226	pathogenic	-1.169	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
S/Y	0.7518	likely_pathogenic	0.7845	pathogenic	-0.77	Destabilizing	0.997	D	0.743	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.