TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6324	19195;19196;19197	chr2:178729068;178729067;178729066	chr2:179593795;179593794;179593793
N2AB	6007	18244;18245;18246	chr2:178729068;178729067;178729066	chr2:179593795;179593794;179593793
N2A	5080	15463;15464;15465	chr2:178729068;178729067;178729066	chr2:179593795;179593794;179593793
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-47
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.4384
• 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/N	None	None	0.175	N	0.4	0.172	0.298745278005	gnomAD-4.0.0	3.42357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49911E-06	0	0
T/S	rs2079898671	None	0.001	N	0.202	0.075	0.186928172975	gnomAD-4.0.0	1.36943E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79965E-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
T/A	0.0853	likely_benign	0.0846	benign	-0.904	Destabilizing	None	N	0.201	neutral	N	0.513510991	None	None	N
T/C	0.3724	ambiguous	0.3853	ambiguous	-0.532	Destabilizing	0.667	D	0.53	neutral	None	None	None	None	N
T/D	0.3051	likely_benign	0.3206	benign	-0.343	Destabilizing	0.22	N	0.438	neutral	None	None	None	None	N
T/E	0.2383	likely_benign	0.2498	benign	-0.267	Destabilizing	0.055	N	0.393	neutral	None	None	None	None	N
T/F	0.1661	likely_benign	0.1697	benign	-0.704	Destabilizing	0.497	N	0.624	neutral	None	None	None	None	N
T/G	0.2625	likely_benign	0.2733	benign	-1.246	Destabilizing	0.055	N	0.429	neutral	None	None	None	None	N
T/H	0.185	likely_benign	0.1831	benign	-1.399	Destabilizing	0.667	D	0.571	neutral	None	None	None	None	N
T/I	0.1072	likely_benign	0.1107	benign	-0.06	Destabilizing	0.001	N	0.22	neutral	D	0.524056059	None	None	N
T/K	0.1692	likely_benign	0.1678	benign	-0.687	Destabilizing	0.055	N	0.41	neutral	None	None	None	None	N
T/L	0.0847	likely_benign	0.0843	benign	-0.06	Destabilizing	0.009	N	0.327	neutral	None	None	None	None	N
T/M	0.0844	likely_benign	0.0866	benign	0.067	Stabilizing	0.497	N	0.535	neutral	None	None	None	None	N
T/N	0.116	likely_benign	0.1186	benign	-0.84	Destabilizing	0.175	N	0.4	neutral	N	0.497355485	None	None	N
T/P	0.5803	likely_pathogenic	0.6046	pathogenic	-0.307	Destabilizing	0.301	N	0.49	neutral	D	0.534324463	None	None	N
T/Q	0.1772	likely_benign	0.1774	benign	-0.831	Destabilizing	0.005	N	0.231	neutral	None	None	None	None	N
T/R	0.1324	likely_benign	0.1296	benign	-0.605	Destabilizing	0.22	N	0.487	neutral	None	None	None	None	N
T/S	0.0923	likely_benign	0.0916	benign	-1.148	Destabilizing	0.001	N	0.202	neutral	N	0.452670389	None	None	N
T/V	0.0996	likely_benign	0.1001	benign	-0.307	Destabilizing	None	N	0.213	neutral	None	None	None	None	N
T/W	0.4556	ambiguous	0.4653	ambiguous	-0.695	Destabilizing	0.958	D	0.579	neutral	None	None	None	None	N
T/Y	0.1927	likely_benign	0.198	benign	-0.434	Destabilizing	0.667	D	0.617	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.