TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25334	76225;76226;76227	chr2:178570132;178570131;178570130	chr2:179434859;179434858;179434857
N2AB	23693	71302;71303;71304	chr2:178570132;178570131;178570130	chr2:179434859;179434858;179434857
N2A	22766	68521;68522;68523	chr2:178570132;178570131;178570130	chr2:179434859;179434858;179434857
N2B	16269	49030;49031;49032	chr2:178570132;178570131;178570130	chr2:179434859;179434858;179434857
Novex-1	16394	49405;49406;49407	chr2:178570132;178570131;178570130	chr2:179434859;179434858;179434857
Novex-2	16461	49606;49607;49608	chr2:178570132;178570131;178570130	chr2:179434859;179434858;179434857
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: Fn3-72
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3587
• 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/R	None	None	0.97	N	0.621	0.438	0.371718192555	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1336	likely_benign	0.1462	benign	-0.501	Destabilizing	0.559	D	0.623	neutral	None	None	None	None	I
S/C	0.1022	likely_benign	0.1162	benign	-0.308	Destabilizing	0.032	N	0.539	neutral	N	0.492123293	None	None	I
S/D	0.8367	likely_pathogenic	0.8218	pathogenic	-0.235	Destabilizing	0.754	D	0.656	neutral	None	None	None	None	I
S/E	0.8847	likely_pathogenic	0.873	pathogenic	-0.308	Destabilizing	0.86	D	0.667	neutral	None	None	None	None	I
S/F	0.6139	likely_pathogenic	0.6052	pathogenic	-0.984	Destabilizing	0.978	D	0.709	prob.delet.	None	None	None	None	I
S/G	0.2142	likely_benign	0.226	benign	-0.655	Destabilizing	0.822	D	0.605	neutral	N	0.480528909	None	None	I
S/H	0.6288	likely_pathogenic	0.6149	pathogenic	-1.218	Destabilizing	0.994	D	0.618	neutral	None	None	None	None	I
S/I	0.6022	likely_pathogenic	0.5653	pathogenic	-0.215	Destabilizing	0.942	D	0.704	prob.neutral	N	0.501718399	None	None	I
S/K	0.9322	likely_pathogenic	0.9065	pathogenic	-0.597	Destabilizing	0.86	D	0.669	neutral	None	None	None	None	I
S/L	0.2739	likely_benign	0.2616	benign	-0.215	Destabilizing	0.754	D	0.679	prob.neutral	None	None	None	None	I
S/M	0.3962	ambiguous	0.4004	ambiguous	0.211	Stabilizing	0.998	D	0.619	neutral	None	None	None	None	I
S/N	0.2218	likely_benign	0.2152	benign	-0.374	Destabilizing	0.058	N	0.447	neutral	N	0.485918322	None	None	I
S/P	0.9872	likely_pathogenic	0.9838	pathogenic	-0.28	Destabilizing	0.993	D	0.619	neutral	None	None	None	None	I
S/Q	0.7673	likely_pathogenic	0.7533	pathogenic	-0.68	Destabilizing	0.978	D	0.641	neutral	None	None	None	None	I
S/R	0.8782	likely_pathogenic	0.8456	pathogenic	-0.357	Destabilizing	0.97	D	0.621	neutral	N	0.482902901	None	None	I
S/T	0.22	likely_benign	0.2161	benign	-0.45	Destabilizing	0.822	D	0.646	neutral	N	0.47365019	None	None	I
S/V	0.476	ambiguous	0.4697	ambiguous	-0.28	Destabilizing	0.956	D	0.666	neutral	None	None	None	None	I
S/W	0.7824	likely_pathogenic	0.7461	pathogenic	-0.949	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	I
S/Y	0.5495	ambiguous	0.5083	ambiguous	-0.683	Destabilizing	0.993	D	0.705	prob.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.