TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30972	93139;93140;93141	chr2:178548712;178548711;178548710	chr2:179413439;179413438;179413437
N2AB	29331	88216;88217;88218	chr2:178548712;178548711;178548710	chr2:179413439;179413438;179413437
N2A	28404	85435;85436;85437	chr2:178548712;178548711;178548710	chr2:179413439;179413438;179413437
N2B	21907	65944;65945;65946	chr2:178548712;178548711;178548710	chr2:179413439;179413438;179413437
Novex-1	22032	66319;66320;66321	chr2:178548712;178548711;178548710	chr2:179413439;179413438;179413437
Novex-2	22099	66520;66521;66522	chr2:178548712;178548711;178548710	chr2:179413439;179413438;179413437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-150
• Domain position: 46
• Structural Position: 123
• Q(SASA): 0.2365
• 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
I/S	rs773430543	-1.7	0.998	D	0.573	0.691	0.8154997	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/S	rs773430543	-1.7	0.998	D	0.573	0.691	0.8154997	gnomAD-4.0.0	3.18239E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86541E-05	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
I/A	0.7401	likely_pathogenic	0.7448	pathogenic	-1.751	Destabilizing	0.992	D	0.391	neutral	None	None	None	None	I
I/C	0.8245	likely_pathogenic	0.8196	pathogenic	-1.083	Destabilizing	1.0	D	0.568	neutral	None	None	None	None	I
I/D	0.9609	likely_pathogenic	0.9612	pathogenic	-1.001	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
I/E	0.8962	likely_pathogenic	0.9036	pathogenic	-0.98	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
I/F	0.33	likely_benign	0.3416	ambiguous	-1.294	Destabilizing	0.998	D	0.491	neutral	N	0.50282645	None	None	I
I/G	0.9163	likely_pathogenic	0.9189	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
I/H	0.8359	likely_pathogenic	0.8448	pathogenic	-1.318	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
I/K	0.7527	likely_pathogenic	0.7735	pathogenic	-1.051	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
I/L	0.2229	likely_benign	0.2241	benign	-0.854	Destabilizing	0.889	D	0.341	neutral	N	0.4979117	None	None	I
I/M	0.1874	likely_benign	0.191	benign	-0.658	Destabilizing	0.998	D	0.514	neutral	N	0.49802706	None	None	I
I/N	0.6985	likely_pathogenic	0.7065	pathogenic	-0.88	Destabilizing	0.999	D	0.687	prob.neutral	D	0.5454177	None	None	I
I/P	0.971	likely_pathogenic	0.9686	pathogenic	-1.122	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
I/Q	0.7995	likely_pathogenic	0.8081	pathogenic	-1.028	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
I/R	0.6787	likely_pathogenic	0.697	pathogenic	-0.512	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
I/S	0.6771	likely_pathogenic	0.6795	pathogenic	-1.559	Destabilizing	0.998	D	0.573	neutral	D	0.52655303	None	None	I
I/T	0.4792	ambiguous	0.4925	ambiguous	-1.407	Destabilizing	0.989	D	0.496	neutral	N	0.5099168	None	None	I
I/V	0.1044	likely_benign	0.1059	benign	-1.122	Destabilizing	0.333	N	0.219	neutral	N	0.49925083	None	None	I
I/W	0.9197	likely_pathogenic	0.9182	pathogenic	-1.36	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
I/Y	0.7633	likely_pathogenic	0.7724	pathogenic	-1.123	Destabilizing	1.0	D	0.547	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.