TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6095	18508;18509;18510	chr2:178730117;178730116;178730115	chr2:179594844;179594843;179594842
N2AB	5778	17557;17558;17559	chr2:178730117;178730116;178730115	chr2:179594844;179594843;179594842
N2A	4851	14776;14777;14778	chr2:178730117;178730116;178730115	chr2:179594844;179594843;179594842
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-44
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1161
• 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/I	None	None	0.029	N	0.691	0.225	0.594903367923	gnomAD-4.0.0	7.34788E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.53854E-07	0	0
S/N	None	None	0.055	N	0.565	0.247	0.220303561663	gnomAD-4.0.0	2.93915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.81542E-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	0.0951	likely_benign	0.0886	benign	-0.573	Destabilizing	0.007	N	0.359	neutral	None	None	None	None	N
S/C	0.0549	likely_benign	0.0541	benign	-0.209	Destabilizing	None	N	0.387	neutral	N	0.444363124	None	None	N
S/D	0.6346	likely_pathogenic	0.5917	pathogenic	-0.404	Destabilizing	0.072	N	0.569	neutral	None	None	None	None	N
S/E	0.7526	likely_pathogenic	0.7081	pathogenic	-0.283	Destabilizing	0.072	N	0.571	neutral	None	None	None	None	N
S/F	0.3364	likely_benign	0.2852	benign	-0.453	Destabilizing	0.356	N	0.742	deleterious	None	None	None	None	N
S/G	0.1093	likely_benign	0.096	benign	-0.935	Destabilizing	0.024	N	0.497	neutral	N	0.509712521	None	None	N
S/H	0.5776	likely_pathogenic	0.5143	ambiguous	-1.286	Destabilizing	0.628	D	0.694	prob.neutral	None	None	None	None	N
S/I	0.2674	likely_benign	0.2474	benign	0.317	Stabilizing	0.029	N	0.691	prob.neutral	N	0.493076297	None	None	N
S/K	0.918	likely_pathogenic	0.8822	pathogenic	-0.205	Destabilizing	0.072	N	0.568	neutral	None	None	None	None	N
S/L	0.1996	likely_benign	0.1799	benign	0.317	Stabilizing	0.016	N	0.667	neutral	None	None	None	None	N
S/M	0.2924	likely_benign	0.2686	benign	0.272	Stabilizing	0.356	N	0.703	prob.neutral	None	None	None	None	N
S/N	0.2465	likely_benign	0.2323	benign	-0.54	Destabilizing	0.055	N	0.565	neutral	N	0.500811751	None	None	N
S/P	0.8964	likely_pathogenic	0.9085	pathogenic	0.056	Stabilizing	0.136	N	0.748	deleterious	None	None	None	None	N
S/Q	0.7123	likely_pathogenic	0.6699	pathogenic	-0.412	Destabilizing	0.356	N	0.665	neutral	None	None	None	None	N
S/R	0.8448	likely_pathogenic	0.7922	pathogenic	-0.445	Destabilizing	0.171	N	0.748	deleterious	N	0.489201957	None	None	N
S/T	0.0921	likely_benign	0.087	benign	-0.379	Destabilizing	None	N	0.209	neutral	N	0.508411816	None	None	N
S/V	0.213	likely_benign	0.208	benign	0.056	Stabilizing	0.016	N	0.667	neutral	None	None	None	None	N
S/W	0.4941	ambiguous	0.441	ambiguous	-0.611	Destabilizing	0.864	D	0.719	prob.delet.	None	None	None	None	N
S/Y	0.2913	likely_benign	0.2443	benign	-0.208	Destabilizing	0.356	N	0.739	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.