TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13783	41572;41573;41574	chr2:178636224;178636223;178636222	chr2:179500951;179500950;179500949
N2AB	12142	36649;36650;36651	chr2:178636224;178636223;178636222	chr2:179500951;179500950;179500949
N2A	11215	33868;33869;33870	chr2:178636224;178636223;178636222	chr2:179500951;179500950;179500949
N2B	4718	14377;14378;14379	chr2:178636224;178636223;178636222	chr2:179500951;179500950;179500949
Novex-1	4843	14752;14753;14754	chr2:178636224;178636223;178636222	chr2:179500951;179500950;179500949
Novex-2	4910	14953;14954;14955	chr2:178636224;178636223;178636222	chr2:179500951;179500950;179500949
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-88
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2339
• 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	rs2060418351	None	0.826	N	0.394	0.125	0.381409048467	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs2060418351	None	0.826	N	0.394	0.125	0.381409048467	gnomAD-4.0.0	6.5754E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47059E-05	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	0.4846	ambiguous	0.6928	pathogenic	-1.004	Destabilizing	0.826	D	0.394	neutral	N	0.344138718	None	None	N
V/C	0.8949	likely_pathogenic	0.9354	pathogenic	-0.709	Destabilizing	0.999	D	0.478	neutral	None	None	None	None	N
V/D	0.7753	likely_pathogenic	0.9256	pathogenic	-0.626	Destabilizing	0.991	D	0.673	prob.neutral	None	None	None	None	N
V/E	0.5482	ambiguous	0.7666	pathogenic	-0.679	Destabilizing	0.92	D	0.611	neutral	N	0.366708356	None	None	N
V/F	0.3747	ambiguous	0.5608	ambiguous	-0.818	Destabilizing	0.982	D	0.523	neutral	None	None	None	None	N
V/G	0.5187	ambiguous	0.7298	pathogenic	-1.244	Destabilizing	0.959	D	0.673	prob.neutral	N	0.320374607	None	None	N
V/H	0.8516	likely_pathogenic	0.9371	pathogenic	-0.642	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
V/I	0.0962	likely_benign	0.1086	benign	-0.48	Destabilizing	0.061	N	0.107	neutral	N	0.352263308	None	None	N
V/K	0.6355	likely_pathogenic	0.8265	pathogenic	-0.844	Destabilizing	0.884	D	0.626	neutral	None	None	None	None	N
V/L	0.3197	likely_benign	0.455	ambiguous	-0.48	Destabilizing	0.509	D	0.284	neutral	N	0.346381716	None	None	N
V/M	0.2979	likely_benign	0.4342	ambiguous	-0.415	Destabilizing	0.579	D	0.285	neutral	None	None	None	None	N
V/N	0.6407	likely_pathogenic	0.8117	pathogenic	-0.596	Destabilizing	0.991	D	0.661	prob.neutral	None	None	None	None	N
V/P	0.9481	likely_pathogenic	0.975	pathogenic	-0.618	Destabilizing	0.997	D	0.625	neutral	None	None	None	None	N
V/Q	0.5556	ambiguous	0.7282	pathogenic	-0.811	Destabilizing	0.982	D	0.619	neutral	None	None	None	None	N
V/R	0.5544	ambiguous	0.7507	pathogenic	-0.263	Destabilizing	0.1	N	0.43	neutral	None	None	None	None	N
V/S	0.5057	ambiguous	0.7101	pathogenic	-1.071	Destabilizing	0.884	D	0.575	neutral	None	None	None	None	N
V/T	0.354	ambiguous	0.5199	ambiguous	-1.02	Destabilizing	0.17	N	0.228	neutral	None	None	None	None	N
V/W	0.9432	likely_pathogenic	0.9784	pathogenic	-0.927	Destabilizing	0.999	D	0.696	prob.delet.	None	None	None	None	N
V/Y	0.8339	likely_pathogenic	0.9192	pathogenic	-0.652	Destabilizing	0.997	D	0.521	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.