TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6397	19414;19415;19416	chr2:178728737;178728736;178728735	chr2:179593464;179593463;179593462
N2AB	6080	18463;18464;18465	chr2:178728737;178728736;178728735	chr2:179593464;179593463;179593462
N2A	5153	15682;15683;15684	chr2:178728737;178728736;178728735	chr2:179593464;179593463;179593462
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: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-48
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5529
• 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
T/M	rs199564845	0.039	1.0	D	0.633	0.422	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	1.29349E-04	8.74E-05	None	0	0	None	0	None	0	1.78E-05	0
T/M	rs199564845	0.039	1.0	D	0.633	0.422	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	4.83E-05	1.96489E-04	0	0	0	None	0	0	5.88E-05	0	0
T/M	rs199564845	0.039	1.0	D	0.633	0.422	None	gnomAD-4.0.0	2.79825E-05	None	None	None	None	N	None	9.35404E-05	8.35478E-05	None	0	0	None	1.56392E-05	0	2.63781E-05	0	1.60679E-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
T/A	0.2264	likely_benign	0.2155	benign	-0.547	Destabilizing	0.981	D	0.544	neutral	N	0.509334536	None	None	N
T/C	0.8545	likely_pathogenic	0.7967	pathogenic	-0.364	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
T/D	0.8184	likely_pathogenic	0.8555	pathogenic	0.17	Stabilizing	0.999	D	0.607	neutral	None	None	None	None	N
T/E	0.6583	likely_pathogenic	0.7182	pathogenic	0.147	Stabilizing	0.999	D	0.602	neutral	None	None	None	None	N
T/F	0.6546	likely_pathogenic	0.7038	pathogenic	-0.702	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/G	0.6124	likely_pathogenic	0.627	pathogenic	-0.772	Destabilizing	0.997	D	0.615	neutral	None	None	None	None	N
T/H	0.7021	likely_pathogenic	0.714	pathogenic	-1.005	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/I	0.5262	ambiguous	0.623	pathogenic	-0.055	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
T/K	0.4007	ambiguous	0.4969	ambiguous	-0.543	Destabilizing	1.0	D	0.609	neutral	N	0.521031609	None	None	N
T/L	0.2086	likely_benign	0.2564	benign	-0.055	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
T/M	0.1471	likely_benign	0.1773	benign	0.061	Stabilizing	1.0	D	0.633	neutral	D	0.534155622	None	None	N
T/N	0.434	ambiguous	0.4588	ambiguous	-0.411	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
T/P	0.4019	ambiguous	0.3651	ambiguous	-0.187	Destabilizing	0.999	D	0.62	neutral	D	0.526882933	None	None	N
T/Q	0.4952	ambiguous	0.5439	ambiguous	-0.564	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
T/R	0.3296	likely_benign	0.3843	ambiguous	-0.305	Destabilizing	1.0	D	0.615	neutral	D	0.523071837	None	None	N
T/S	0.3	likely_benign	0.2849	benign	-0.687	Destabilizing	0.905	D	0.376	neutral	D	0.528880302	None	None	N
T/V	0.3782	ambiguous	0.4429	ambiguous	-0.187	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
T/W	0.8839	likely_pathogenic	0.8931	pathogenic	-0.67	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/Y	0.7705	likely_pathogenic	0.7851	pathogenic	-0.422	Destabilizing	1.0	D	0.728	prob.delet.	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.