TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16002	48229;48230;48231	chr2:178616885;178616884;178616883	chr2:179481612;179481611;179481610
N2AB	14361	43306;43307;43308	chr2:178616885;178616884;178616883	chr2:179481612;179481611;179481610
N2A	13434	40525;40526;40527	chr2:178616885;178616884;178616883	chr2:179481612;179481611;179481610
N2B	6937	21034;21035;21036	chr2:178616885;178616884;178616883	chr2:179481612;179481611;179481610
Novex-1	7062	21409;21410;21411	chr2:178616885;178616884;178616883	chr2:179481612;179481611;179481610
Novex-2	7129	21610;21611;21612	chr2:178616885;178616884;178616883	chr2:179481612;179481611;179481610
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-109
• Domain position: 35
• Structural Position: 56
• Q(SASA): 0.7065
• 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
V/A	None	None	0.001	N	0.095	0.082	0.468168183122	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
V/A	0.1409	likely_benign	0.1375	benign	-0.687	Destabilizing	0.001	N	0.095	neutral	N	0.505806433	None	None	N
V/C	0.6028	likely_pathogenic	0.5823	pathogenic	-0.545	Destabilizing	0.958	D	0.372	neutral	None	None	None	None	N
V/D	0.2015	likely_benign	0.1789	benign	-0.601	Destabilizing	0.124	N	0.391	neutral	None	None	None	None	N
V/E	0.1392	likely_benign	0.1314	benign	-0.715	Destabilizing	None	N	0.175	neutral	N	0.44950345	None	None	N
V/F	0.1685	likely_benign	0.1498	benign	-0.875	Destabilizing	0.331	N	0.393	neutral	None	None	None	None	N
V/G	0.1834	likely_benign	0.1684	benign	-0.847	Destabilizing	0.096	N	0.384	neutral	D	0.540318682	None	None	N
V/H	0.3743	ambiguous	0.3432	ambiguous	-0.46	Destabilizing	0.667	D	0.373	neutral	None	None	None	None	N
V/I	0.081	likely_benign	0.0832	benign	-0.406	Destabilizing	0.042	N	0.338	neutral	N	0.510326482	None	None	N
V/K	0.1631	likely_benign	0.1514	benign	-0.615	Destabilizing	0.124	N	0.367	neutral	None	None	None	None	N
V/L	0.1556	likely_benign	0.1417	benign	-0.406	Destabilizing	0.001	N	0.109	neutral	N	0.508829464	None	None	N
V/M	0.1338	likely_benign	0.1283	benign	-0.306	Destabilizing	0.497	N	0.388	neutral	None	None	None	None	N
V/N	0.1487	likely_benign	0.1392	benign	-0.265	Destabilizing	0.497	N	0.399	neutral	None	None	None	None	N
V/P	0.2191	likely_benign	0.1982	benign	-0.464	Destabilizing	0.667	D	0.38	neutral	None	None	None	None	N
V/Q	0.1807	likely_benign	0.1708	benign	-0.551	Destabilizing	0.331	N	0.382	neutral	None	None	None	None	N
V/R	0.1855	likely_benign	0.1679	benign	-0.04	Destabilizing	0.497	N	0.404	neutral	None	None	None	None	N
V/S	0.1505	likely_benign	0.1396	benign	-0.613	Destabilizing	0.011	N	0.197	neutral	None	None	None	None	N
V/T	0.1344	likely_benign	0.1311	benign	-0.631	Destabilizing	0.055	N	0.273	neutral	None	None	None	None	N
V/W	0.7362	likely_pathogenic	0.6885	pathogenic	-0.958	Destabilizing	0.958	D	0.429	neutral	None	None	None	None	N
V/Y	0.3996	ambiguous	0.3634	ambiguous	-0.668	Destabilizing	0.667	D	0.386	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.