TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27362	82309;82310;82311	chr2:178564048;178564047;178564046	chr2:179428775;179428774;179428773
N2AB	25721	77386;77387;77388	chr2:178564048;178564047;178564046	chr2:179428775;179428774;179428773
N2A	24794	74605;74606;74607	chr2:178564048;178564047;178564046	chr2:179428775;179428774;179428773
N2B	18297	55114;55115;55116	chr2:178564048;178564047;178564046	chr2:179428775;179428774;179428773
Novex-1	18422	55489;55490;55491	chr2:178564048;178564047;178564046	chr2:179428775;179428774;179428773
Novex-2	18489	55690;55691;55692	chr2:178564048;178564047;178564046	chr2:179428775;179428774;179428773
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-140
• Domain position: 85
• Structural Position: 172
• Q(SASA): 0.0347
• 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
I/V	rs886039181	-1.629	0.011	N	0.233	0.062	0.381580015636	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	1.57E-05	0
I/V	rs886039181	-1.629	0.011	N	0.233	0.062	0.381580015636	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs886039181	-1.629	0.011	N	0.233	0.062	0.381580015636	gnomAD-4.0.0	1.3014E-05	None	None	None	None	N	None	4.00502E-05	0	None	0	0	None	0	0	1.441E-05	0	1.60108E-05

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	0.7522	likely_pathogenic	0.8136	pathogenic	-2.51	Highly Destabilizing	0.845	D	0.683	prob.neutral	None	None	None	None	N
I/C	0.7791	likely_pathogenic	0.8403	pathogenic	-1.766	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
I/D	0.9941	likely_pathogenic	0.996	pathogenic	-2.894	Highly Destabilizing	0.996	D	0.818	deleterious	None	None	None	None	N
I/E	0.9833	likely_pathogenic	0.9885	pathogenic	-2.6	Highly Destabilizing	0.987	D	0.817	deleterious	None	None	None	None	N
I/F	0.2213	likely_benign	0.2946	benign	-1.509	Destabilizing	0.967	D	0.722	prob.delet.	N	0.474261957	None	None	N
I/G	0.9576	likely_pathogenic	0.9724	pathogenic	-3.108	Highly Destabilizing	0.987	D	0.813	deleterious	None	None	None	None	N
I/H	0.9556	likely_pathogenic	0.9726	pathogenic	-2.638	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
I/K	0.9564	likely_pathogenic	0.972	pathogenic	-2.005	Highly Destabilizing	0.987	D	0.814	deleterious	None	None	None	None	N
I/L	0.1607	likely_benign	0.1825	benign	-0.747	Destabilizing	0.426	N	0.439	neutral	N	0.504080644	None	None	N
I/M	0.1517	likely_benign	0.1839	benign	-0.733	Destabilizing	0.983	D	0.694	prob.neutral	N	0.506585423	None	None	N
I/N	0.9217	likely_pathogenic	0.9458	pathogenic	-2.552	Highly Destabilizing	0.994	D	0.828	deleterious	N	0.513675767	None	None	N
I/P	0.9892	likely_pathogenic	0.992	pathogenic	-1.32	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
I/Q	0.9534	likely_pathogenic	0.9698	pathogenic	-2.272	Highly Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	N
I/R	0.9275	likely_pathogenic	0.955	pathogenic	-1.947	Destabilizing	0.987	D	0.832	deleterious	None	None	None	None	N
I/S	0.8885	likely_pathogenic	0.9238	pathogenic	-3.236	Highly Destabilizing	0.983	D	0.759	deleterious	N	0.494557554	None	None	N
I/T	0.8225	likely_pathogenic	0.8808	pathogenic	-2.771	Highly Destabilizing	0.892	D	0.744	deleterious	D	0.535675775	None	None	N
I/V	0.069	likely_benign	0.0716	benign	-1.32	Destabilizing	0.011	N	0.233	neutral	N	0.427217371	None	None	N
I/W	0.9535	likely_pathogenic	0.9704	pathogenic	-1.897	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
I/Y	0.8291	likely_pathogenic	0.8772	pathogenic	-1.592	Destabilizing	0.987	D	0.764	deleterious	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.