TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17463	52612;52613;52614	chr2:178608624;178608623;178608622	chr2:179473351;179473350;179473349
N2AB	15822	47689;47690;47691	chr2:178608624;178608623;178608622	chr2:179473351;179473350;179473349
N2A	14895	44908;44909;44910	chr2:178608624;178608623;178608622	chr2:179473351;179473350;179473349
N2B	8398	25417;25418;25419	chr2:178608624;178608623;178608622	chr2:179473351;179473350;179473349
Novex-1	8523	25792;25793;25794	chr2:178608624;178608623;178608622	chr2:179473351;179473350;179473349
Novex-2	8590	25993;25994;25995	chr2:178608624;178608623;178608622	chr2:179473351;179473350;179473349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-14
• Domain position: 95
• Structural Position: 128
• Q(SASA): 0.4209
• 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
V/A	rs2055509870	None	0.002	N	0.217	0.066	0.180583059064	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs2055509870	None	0.002	N	0.217	0.066	0.180583059064	gnomAD-4.0.0	6.57713E-06	None	None	None	None	N	None	2.41289E-05	0	None	0	0	None	0	0	0	0	0
V/M	None	None	0.001	N	0.223	0.112	0.0806252709748	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

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
V/A	0.1438	likely_benign	0.1294	benign	-0.892	Destabilizing	0.002	N	0.217	neutral	N	0.515494425	None	None	N
V/C	0.5725	likely_pathogenic	0.5594	ambiguous	-0.797	Destabilizing	0.204	N	0.299	neutral	None	None	None	None	N
V/D	0.3289	likely_benign	0.3073	benign	-0.43	Destabilizing	0.018	N	0.538	neutral	None	None	None	None	N
V/E	0.1832	likely_benign	0.1789	benign	-0.473	Destabilizing	None	N	0.464	neutral	N	0.496465947	None	None	N
V/F	0.1552	likely_benign	0.1482	benign	-0.711	Destabilizing	0.018	N	0.513	neutral	None	None	None	None	N
V/G	0.2906	likely_benign	0.24	benign	-1.139	Destabilizing	0.013	N	0.478	neutral	N	0.516534575	None	None	N
V/H	0.3775	ambiguous	0.3745	ambiguous	-0.566	Destabilizing	0.204	N	0.399	neutral	None	None	None	None	N
V/I	0.0673	likely_benign	0.0656	benign	-0.35	Destabilizing	None	N	0.049	neutral	None	None	None	None	N
V/K	0.2007	likely_benign	0.1977	benign	-0.769	Destabilizing	0.018	N	0.419	neutral	None	None	None	None	N
V/L	0.1034	likely_benign	0.1043	benign	-0.35	Destabilizing	None	N	0.055	neutral	N	0.462622732	None	None	N
V/M	0.1146	likely_benign	0.1062	benign	-0.412	Destabilizing	0.001	N	0.223	neutral	N	0.516534575	None	None	N
V/N	0.2401	likely_benign	0.225	benign	-0.562	Destabilizing	0.035	N	0.581	neutral	None	None	None	None	N
V/P	0.3564	ambiguous	0.3567	ambiguous	-0.494	Destabilizing	0.068	N	0.543	neutral	None	None	None	None	N
V/Q	0.1992	likely_benign	0.1966	benign	-0.729	Destabilizing	0.018	N	0.571	neutral	None	None	None	None	N
V/R	0.1876	likely_benign	0.1861	benign	-0.263	Destabilizing	0.035	N	0.555	neutral	None	None	None	None	N
V/S	0.1892	likely_benign	0.1695	benign	-1.06	Destabilizing	None	N	0.423	neutral	None	None	None	None	N
V/T	0.0995	likely_benign	0.0905	benign	-0.986	Destabilizing	None	N	0.095	neutral	None	None	None	None	N
V/W	0.6446	likely_pathogenic	0.6339	pathogenic	-0.828	Destabilizing	0.747	D	0.433	neutral	None	None	None	None	N
V/Y	0.4066	ambiguous	0.3998	ambiguous	-0.537	Destabilizing	0.204	N	0.505	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.