TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6353	19282;19283;19284	chr2:178728981;178728980;178728979	chr2:179593708;179593707;179593706
N2AB	6036	18331;18332;18333	chr2:178728981;178728980;178728979	chr2:179593708;179593707;179593706
N2A	5109	15550;15551;15552	chr2:178728981;178728980;178728979	chr2:179593708;179593707;179593706
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-47
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.3015
• 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
S/R	None	None	0.055	N	0.475	0.07	0.0482279557977	gnomAD-4.0.0	1.36902E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-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
S/A	0.066	likely_benign	0.0654	benign	-0.752	Destabilizing	None	N	0.083	neutral	None	None	None	None	N
S/C	0.1093	likely_benign	0.106	benign	-0.513	Destabilizing	0.295	N	0.407	neutral	N	0.492865357	None	None	N
S/D	0.1603	likely_benign	0.132	benign	-0.551	Destabilizing	0.038	N	0.275	neutral	None	None	None	None	N
S/E	0.222	likely_benign	0.196	benign	-0.58	Destabilizing	0.031	N	0.276	neutral	None	None	None	None	N
S/F	0.1099	likely_benign	0.1062	benign	-1.141	Destabilizing	0.214	N	0.48	neutral	None	None	None	None	N
S/G	0.0941	likely_benign	0.0871	benign	-0.961	Destabilizing	0.012	N	0.282	neutral	N	0.482586999	None	None	N
S/H	0.1554	likely_benign	0.1371	benign	-1.538	Destabilizing	0.001	N	0.285	neutral	None	None	None	None	N
S/I	0.1248	likely_benign	0.1122	benign	-0.308	Destabilizing	0.029	N	0.451	neutral	N	0.492865357	None	None	N
S/K	0.263	likely_benign	0.2295	benign	-0.787	Destabilizing	0.072	N	0.279	neutral	None	None	None	None	N
S/L	0.0752	likely_benign	0.075	benign	-0.308	Destabilizing	0.006	N	0.372	neutral	None	None	None	None	N
S/M	0.1093	likely_benign	0.1021	benign	0.171	Stabilizing	0.002	N	0.352	neutral	None	None	None	None	N
S/N	0.0843	likely_benign	0.0739	benign	-0.745	Destabilizing	None	N	0.123	neutral	N	0.431173956	None	None	N
S/P	0.4425	ambiguous	0.4096	ambiguous	-0.424	Destabilizing	0.072	N	0.458	neutral	None	None	None	None	N
S/Q	0.2304	likely_benign	0.1992	benign	-0.978	Destabilizing	0.072	N	0.353	neutral	None	None	None	None	N
S/R	0.2121	likely_benign	0.1884	benign	-0.605	Destabilizing	0.055	N	0.475	neutral	N	0.445588835	None	None	N
S/T	0.0697	likely_benign	0.0665	benign	-0.753	Destabilizing	None	N	0.155	neutral	N	0.453174127	None	None	N
S/V	0.1154	likely_benign	0.1095	benign	-0.424	Destabilizing	0.001	N	0.259	neutral	None	None	None	None	N
S/W	0.1857	likely_benign	0.1708	benign	-1.117	Destabilizing	0.864	D	0.475	neutral	None	None	None	None	N
S/Y	0.0979	likely_benign	0.0917	benign	-0.85	Destabilizing	0.214	N	0.485	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.