TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24054	72385;72386;72387	chr2:178573972;178573971;178573970	chr2:179438699;179438698;179438697
N2AB	22413	67462;67463;67464	chr2:178573972;178573971;178573970	chr2:179438699;179438698;179438697
N2A	21486	64681;64682;64683	chr2:178573972;178573971;178573970	chr2:179438699;179438698;179438697
N2B	14989	45190;45191;45192	chr2:178573972;178573971;178573970	chr2:179438699;179438698;179438697
Novex-1	15114	45565;45566;45567	chr2:178573972;178573971;178573970	chr2:179438699;179438698;179438697
Novex-2	15181	45766;45767;45768	chr2:178573972;178573971;178573970	chr2:179438699;179438698;179438697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-131
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.5848
• Predicted PPI site: I

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/L	None	None	0.101	D	0.293	0.285	0.587417723555	gnomAD-4.0.0	1.36877E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79918E-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	0.0705	likely_benign	0.0784	benign	-0.245	Destabilizing	None	N	0.097	neutral	N	0.470317574	None	None	I
S/C	0.117	likely_benign	0.1199	benign	-0.368	Destabilizing	0.836	D	0.307	neutral	None	None	None	None	I
S/D	0.4264	ambiguous	0.4183	ambiguous	0.427	Stabilizing	0.418	N	0.157	neutral	None	None	None	None	I
S/E	0.4494	ambiguous	0.4415	ambiguous	0.372	Stabilizing	0.228	N	0.183	neutral	None	None	None	None	I
S/F	0.1197	likely_benign	0.1289	benign	-0.746	Destabilizing	0.836	D	0.346	neutral	None	None	None	None	I
S/G	0.1173	likely_benign	0.1151	benign	-0.386	Destabilizing	0.129	N	0.219	neutral	None	None	None	None	I
S/H	0.3164	likely_benign	0.2996	benign	-0.689	Destabilizing	0.002	N	0.19	neutral	None	None	None	None	I
S/I	0.1279	likely_benign	0.133	benign	-0.001	Destabilizing	0.418	N	0.321	neutral	None	None	None	None	I
S/K	0.6358	likely_pathogenic	0.6306	pathogenic	-0.322	Destabilizing	0.228	N	0.166	neutral	None	None	None	None	I
S/L	0.0736	likely_benign	0.081	benign	-0.001	Destabilizing	0.101	N	0.293	neutral	D	0.526037571	None	None	I
S/M	0.1482	likely_benign	0.1558	benign	-0.155	Destabilizing	0.94	D	0.307	neutral	None	None	None	None	I
S/N	0.1801	likely_benign	0.17	benign	-0.161	Destabilizing	0.418	N	0.181	neutral	None	None	None	None	I
S/P	0.8779	likely_pathogenic	0.8608	pathogenic	-0.052	Destabilizing	0.523	D	0.342	neutral	N	0.509320901	None	None	I
S/Q	0.4634	ambiguous	0.4547	ambiguous	-0.285	Destabilizing	0.418	N	0.251	neutral	None	None	None	None	I
S/R	0.5268	ambiguous	0.5267	ambiguous	-0.158	Destabilizing	0.418	N	0.295	neutral	None	None	None	None	I
S/T	0.0762	likely_benign	0.0763	benign	-0.236	Destabilizing	0.001	N	0.105	neutral	N	0.447093998	None	None	I
S/V	0.1454	likely_benign	0.1574	benign	-0.052	Destabilizing	0.129	N	0.286	neutral	None	None	None	None	I
S/W	0.2184	likely_benign	0.2347	benign	-0.818	Destabilizing	0.983	D	0.333	neutral	None	None	None	None	I
S/Y	0.1453	likely_benign	0.1522	benign	-0.492	Destabilizing	0.716	D	0.366	neutral	None	None	None	None	I

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.