TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5504	16735;16736;16737	chr2:178732551;178732550;178732549	chr2:179597278;179597277;179597276
N2AB	5187	15784;15785;15786	chr2:178732551;178732550;178732549	chr2:179597278;179597277;179597276
N2A	4260	13003;13004;13005	chr2:178732551;178732550;178732549	chr2:179597278;179597277;179597276
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-38
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1795
• 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	0.625	N	0.423	0.102	0.247872288689	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/G	rs1038822352	None	0.454	N	0.565	0.275	0.391470661076	gnomAD-4.0.0	6.84267E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99496E-07	0	0
E/K	rs2080741049	None	0.801	N	0.434	0.25	0.252162846088	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
E/K	rs2080741049	None	0.801	N	0.434	0.25	0.252162846088	gnomAD-4.0.0	6.57315E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.42507E-05	0	0	0	0
E/Q	None	None	0.891	N	0.463	0.222	0.208000267992	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/V	rs1038822352	-0.05	0.669	N	0.599	0.315	0.508223314113	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/V	rs1038822352	-0.05	0.669	N	0.599	0.315	0.508223314113	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/V	rs1038822352	-0.05	0.669	N	0.599	0.315	0.508223314113	gnomAD-4.0.0	4.95802E-06	None	None	None	None	N	None	9.34405E-05	0	None	0	0	None	0	0	0	0	1.60143E-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	0.1181	likely_benign	0.1222	benign	-1.287	Destabilizing	0.005	N	0.193	neutral	N	0.451827814	None	None	N
E/C	0.7337	likely_pathogenic	0.7477	pathogenic	-0.613	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
E/D	0.172	likely_benign	0.1905	benign	-1.168	Destabilizing	0.625	D	0.423	neutral	N	0.434146131	None	None	N
E/F	0.5931	likely_pathogenic	0.6326	pathogenic	-1.001	Destabilizing	0.016	N	0.47	neutral	None	None	None	None	N
E/G	0.1343	likely_benign	0.1467	benign	-1.627	Destabilizing	0.454	N	0.565	neutral	N	0.421814338	None	None	N
E/H	0.3327	likely_benign	0.3505	ambiguous	-1.221	Destabilizing	0.991	D	0.501	neutral	None	None	None	None	N
E/I	0.281	likely_benign	0.3098	benign	-0.352	Destabilizing	0.949	D	0.647	neutral	None	None	None	None	N
E/K	0.1416	likely_benign	0.1555	benign	-0.657	Destabilizing	0.801	D	0.434	neutral	N	0.435511567	None	None	N
E/L	0.3074	likely_benign	0.3439	ambiguous	-0.352	Destabilizing	0.728	D	0.587	neutral	None	None	None	None	N
E/M	0.3883	ambiguous	0.4151	ambiguous	0.242	Stabilizing	0.991	D	0.639	neutral	None	None	None	None	N
E/N	0.2539	likely_benign	0.2774	benign	-1.031	Destabilizing	0.842	D	0.465	neutral	None	None	None	None	N
E/P	0.815	likely_pathogenic	0.8577	pathogenic	-0.645	Destabilizing	0.974	D	0.566	neutral	None	None	None	None	N
E/Q	0.1026	likely_benign	0.102	benign	-0.952	Destabilizing	0.891	D	0.463	neutral	N	0.442573613	None	None	N
E/R	0.208	likely_benign	0.2216	benign	-0.501	Destabilizing	0.949	D	0.493	neutral	None	None	None	None	N
E/S	0.1583	likely_benign	0.1663	benign	-1.442	Destabilizing	0.029	N	0.108	neutral	None	None	None	None	N
E/T	0.1707	likely_benign	0.1796	benign	-1.14	Destabilizing	0.728	D	0.498	neutral	None	None	None	None	N
E/V	0.1613	likely_benign	0.176	benign	-0.645	Destabilizing	0.669	D	0.599	neutral	N	0.37234831	None	None	N
E/W	0.8013	likely_pathogenic	0.8302	pathogenic	-0.745	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	N
E/Y	0.4962	ambiguous	0.528	ambiguous	-0.714	Destabilizing	0.904	D	0.633	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.