TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17349	52270;52271;52272	chr2:178609265;178609264;178609263	chr2:179473992;179473991;179473990
N2AB	15708	47347;47348;47349	chr2:178609265;178609264;178609263	chr2:179473992;179473991;179473990
N2A	14781	44566;44567;44568	chr2:178609265;178609264;178609263	chr2:179473992;179473991;179473990
N2B	8284	25075;25076;25077	chr2:178609265;178609264;178609263	chr2:179473992;179473991;179473990
Novex-1	8409	25450;25451;25452	chr2:178609265;178609264;178609263	chr2:179473992;179473991;179473990
Novex-2	8476	25651;25652;25653	chr2:178609265;178609264;178609263	chr2:179473992;179473991;179473990
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-112
• Domain position: 99
• Structural Position: 156
• Q(SASA): 0.0882
• 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/M	rs1273982598	-1.769	0.998	N	0.651	0.234	0.530509239904	gnomAD-2.1.1	5.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.46E-05	None	0	0	0
I/M	rs1273982598	-1.769	0.998	N	0.651	0.234	0.530509239904	gnomAD-4.0.0	1.76556E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.75199E-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	0.9427	likely_pathogenic	0.9346	pathogenic	-3.004	Highly Destabilizing	0.992	D	0.762	deleterious	None	None	None	None	N
I/C	0.9589	likely_pathogenic	0.9582	pathogenic	-2.025	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
I/D	0.9993	likely_pathogenic	0.9991	pathogenic	-3.551	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/E	0.9967	likely_pathogenic	0.9957	pathogenic	-3.268	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/F	0.8262	likely_pathogenic	0.7907	pathogenic	-1.729	Destabilizing	0.998	D	0.668	neutral	N	0.483101986	None	None	N
I/G	0.9905	likely_pathogenic	0.9879	pathogenic	-3.569	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/H	0.9981	likely_pathogenic	0.9975	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
I/K	0.9938	likely_pathogenic	0.9924	pathogenic	-2.325	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/L	0.2171	likely_benign	0.2079	benign	-1.314	Destabilizing	0.889	D	0.387	neutral	N	0.470791137	None	None	N
I/M	0.2997	likely_benign	0.2934	benign	-1.315	Destabilizing	0.998	D	0.651	neutral	N	0.454655384	None	None	N
I/N	0.9903	likely_pathogenic	0.9876	pathogenic	-2.865	Highly Destabilizing	0.999	D	0.898	deleterious	N	0.484622923	None	None	N
I/P	0.9958	likely_pathogenic	0.9943	pathogenic	-1.868	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
I/Q	0.9931	likely_pathogenic	0.9916	pathogenic	-2.62	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
I/R	0.9909	likely_pathogenic	0.9891	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
I/S	0.9866	likely_pathogenic	0.9834	pathogenic	-3.466	Highly Destabilizing	0.998	D	0.869	deleterious	N	0.484369434	None	None	N
I/T	0.9774	likely_pathogenic	0.9718	pathogenic	-3.044	Highly Destabilizing	0.989	D	0.764	deleterious	N	0.484115944	None	None	N
I/V	0.1466	likely_benign	0.1398	benign	-1.868	Destabilizing	0.333	N	0.333	neutral	N	0.447279559	None	None	N
I/W	0.9961	likely_pathogenic	0.9948	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/Y	0.9862	likely_pathogenic	0.9834	pathogenic	-1.957	Destabilizing	1.0	D	0.736	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.