TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28046	84361;84362;84363	chr2:178561996;178561995;178561994	chr2:179426723;179426722;179426721
N2AB	26405	79438;79439;79440	chr2:178561996;178561995;178561994	chr2:179426723;179426722;179426721
N2A	25478	76657;76658;76659	chr2:178561996;178561995;178561994	chr2:179426723;179426722;179426721
N2B	18981	57166;57167;57168	chr2:178561996;178561995;178561994	chr2:179426723;179426722;179426721
Novex-1	19106	57541;57542;57543	chr2:178561996;178561995;178561994	chr2:179426723;179426722;179426721
Novex-2	19173	57742;57743;57744	chr2:178561996;178561995;178561994	chr2:179426723;179426722;179426721
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-142
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.2033
• 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
V/F	None	None	0.655	N	0.615	0.186	0.683689280437	gnomAD-4.0.0	5.47506E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19655E-06	0	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
V/A	0.1371	likely_benign	0.1434	benign	-1.7	Destabilizing	None	N	0.16	neutral	N	0.400684131	None	None	I
V/C	0.6517	likely_pathogenic	0.6531	pathogenic	-1.146	Destabilizing	0.836	D	0.597	neutral	None	None	None	None	I
V/D	0.4021	ambiguous	0.4774	ambiguous	-1.876	Destabilizing	0.213	N	0.644	neutral	D	0.52824837	None	None	I
V/E	0.2588	likely_benign	0.2891	benign	-1.779	Destabilizing	0.418	N	0.611	neutral	None	None	None	None	I
V/F	0.1611	likely_benign	0.1669	benign	-1.128	Destabilizing	0.655	D	0.615	neutral	N	0.510009326	None	None	I
V/G	0.2741	likely_benign	0.3206	benign	-2.102	Highly Destabilizing	0.101	N	0.585	neutral	N	0.493578436	None	None	I
V/H	0.4929	ambiguous	0.5174	ambiguous	-1.623	Destabilizing	0.836	D	0.645	neutral	None	None	None	None	I
V/I	0.087	likely_benign	0.0813	benign	-0.648	Destabilizing	0.002	N	0.187	neutral	N	0.474819317	None	None	I
V/K	0.3059	likely_benign	0.3368	benign	-1.542	Destabilizing	0.418	N	0.607	neutral	None	None	None	None	I
V/L	0.1822	likely_benign	0.1675	benign	-0.648	Destabilizing	0.017	N	0.359	neutral	N	0.488921978	None	None	I
V/M	0.1267	likely_benign	0.127	benign	-0.567	Destabilizing	0.716	D	0.586	neutral	None	None	None	None	I
V/N	0.3086	likely_benign	0.344	ambiguous	-1.514	Destabilizing	0.01	N	0.449	neutral	None	None	None	None	I
V/P	0.9068	likely_pathogenic	0.9251	pathogenic	-0.968	Destabilizing	0.836	D	0.624	neutral	None	None	None	None	I
V/Q	0.2905	likely_benign	0.3156	benign	-1.547	Destabilizing	0.836	D	0.629	neutral	None	None	None	None	I
V/R	0.315	likely_benign	0.3593	ambiguous	-1.139	Destabilizing	0.716	D	0.662	neutral	None	None	None	None	I
V/S	0.1883	likely_benign	0.2111	benign	-2.03	Highly Destabilizing	0.129	N	0.555	neutral	None	None	None	None	I
V/T	0.1403	likely_benign	0.1443	benign	-1.804	Destabilizing	0.228	N	0.457	neutral	None	None	None	None	I
V/W	0.8198	likely_pathogenic	0.839	pathogenic	-1.425	Destabilizing	0.983	D	0.663	neutral	None	None	None	None	I
V/Y	0.4819	ambiguous	0.4955	ambiguous	-1.098	Destabilizing	0.836	D	0.615	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.