TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9100	27523;27524;27525	chr2:178712727;178712726;178712725	chr2:179577454;179577453;179577452
N2AB	8783	26572;26573;26574	chr2:178712727;178712726;178712725	chr2:179577454;179577453;179577452
N2A	7856	23791;23792;23793	chr2:178712727;178712726;178712725	chr2:179577454;179577453;179577452
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-76
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1283
• 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
A/S	rs746094812	-0.795	0.012	N	0.429	0.107	0.159798565429	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.28923E-04	None	0	0	0
A/S	rs746094812	-0.795	0.012	N	0.429	0.107	0.159798565429	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
A/S	rs746094812	-0.795	0.012	N	0.429	0.107	0.159798565429	gnomAD-4.0.0	1.48737E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.63522E-04	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
A/C	0.6138	likely_pathogenic	0.6135	pathogenic	-0.664	Destabilizing	0.356	N	0.578	neutral	None	None	None	None	N
A/D	0.1524	likely_benign	0.1569	benign	-0.239	Destabilizing	None	N	0.375	neutral	N	0.490423488	None	None	N
A/E	0.209	likely_benign	0.1979	benign	-0.27	Destabilizing	None	N	0.286	neutral	None	None	None	None	N
A/F	0.3477	ambiguous	0.3121	benign	-0.619	Destabilizing	0.214	N	0.67	neutral	None	None	None	None	N
A/G	0.191	likely_benign	0.1885	benign	-0.765	Destabilizing	0.024	N	0.416	neutral	N	0.500117416	None	None	N
A/H	0.5267	ambiguous	0.4906	ambiguous	-0.847	Destabilizing	0.628	D	0.634	neutral	None	None	None	None	N
A/I	0.1779	likely_benign	0.1733	benign	-0.037	Destabilizing	None	N	0.353	neutral	None	None	None	None	N
A/K	0.4964	ambiguous	0.4632	ambiguous	-0.736	Destabilizing	0.031	N	0.547	neutral	None	None	None	None	N
A/L	0.2049	likely_benign	0.1985	benign	-0.037	Destabilizing	0.016	N	0.523	neutral	None	None	None	None	N
A/M	0.2128	likely_benign	0.204	benign	-0.164	Destabilizing	0.214	N	0.613	neutral	None	None	None	None	N
A/N	0.2198	likely_benign	0.2178	benign	-0.503	Destabilizing	0.038	N	0.613	neutral	None	None	None	None	N
A/P	0.8682	likely_pathogenic	0.8662	pathogenic	-0.157	Destabilizing	0.106	N	0.636	neutral	D	0.528843961	None	None	N
A/Q	0.3801	ambiguous	0.3482	ambiguous	-0.601	Destabilizing	0.072	N	0.635	neutral	None	None	None	None	N
A/R	0.4679	ambiguous	0.4294	ambiguous	-0.507	Destabilizing	0.072	N	0.644	neutral	None	None	None	None	N
A/S	0.0984	likely_benign	0.0977	benign	-0.918	Destabilizing	0.012	N	0.429	neutral	N	0.491265872	None	None	N
A/T	0.0798	likely_benign	0.082	benign	-0.841	Destabilizing	None	N	0.123	neutral	N	0.496559017	None	None	N
A/V	0.0967	likely_benign	0.0912	benign	-0.157	Destabilizing	None	N	0.122	neutral	N	0.49332772	None	None	N
A/W	0.8012	likely_pathogenic	0.7728	pathogenic	-0.949	Destabilizing	0.864	D	0.657	neutral	None	None	None	None	N
A/Y	0.4637	ambiguous	0.4246	ambiguous	-0.505	Destabilizing	0.356	N	0.645	neutral	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.