TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9319	28180;28181;28182	chr2:178711281;178711280;178711279	chr2:179576008;179576007;179576006
N2AB	9002	27229;27230;27231	chr2:178711281;178711280;178711279	chr2:179576008;179576007;179576006
N2A	8075	24448;24449;24450	chr2:178711281;178711280;178711279	chr2:179576008;179576007;179576006
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-79
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2578
• 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/I	None	None	None	None	0.216	0.072	0.296679040009	gnomAD-4.0.0	1.59204E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43542E-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
V/A	0.1077	likely_benign	0.1195	benign	-1.306	Destabilizing	0.019	N	0.309	neutral	None	None	None	None	I
V/C	0.6532	likely_pathogenic	0.6594	pathogenic	-1.001	Destabilizing	0.859	D	0.421	neutral	None	None	None	None	I
V/D	0.2596	likely_benign	0.3067	benign	-0.835	Destabilizing	0.175	N	0.483	neutral	None	None	None	None	I
V/E	0.1837	likely_benign	0.2046	benign	-0.796	Destabilizing	0.055	N	0.397	neutral	None	None	None	None	I
V/F	0.1404	likely_benign	0.1437	benign	-0.882	Destabilizing	0.427	N	0.517	neutral	None	None	None	None	I
V/G	0.1603	likely_benign	0.1768	benign	-1.652	Destabilizing	None	N	0.46	neutral	None	None	None	None	I
V/H	0.301	likely_benign	0.3324	benign	-1.057	Destabilizing	0.667	D	0.481	neutral	None	None	None	None	I
V/I	0.0762	likely_benign	0.0773	benign	-0.453	Destabilizing	None	N	0.216	neutral	None	None	None	None	I
V/K	0.1398	likely_benign	0.1755	benign	-1.064	Destabilizing	0.002	N	0.35	neutral	None	None	None	None	I
V/L	0.1424	likely_benign	0.1535	benign	-0.453	Destabilizing	None	N	0.231	neutral	None	None	None	None	I
V/M	0.1155	likely_benign	0.1182	benign	-0.49	Destabilizing	0.497	N	0.393	neutral	None	None	None	None	I
V/N	0.156	likely_benign	0.1706	benign	-0.97	Destabilizing	0.22	N	0.501	neutral	None	None	None	None	I
V/P	0.6624	likely_pathogenic	0.7672	pathogenic	-0.702	Destabilizing	0.364	N	0.518	neutral	None	None	None	None	I
V/Q	0.1566	likely_benign	0.1834	benign	-1.036	Destabilizing	0.011	N	0.342	neutral	None	None	None	None	I
V/R	0.1211	likely_benign	0.1468	benign	-0.641	Destabilizing	0.001	N	0.427	neutral	None	None	None	None	I
V/S	0.1096	likely_benign	0.1159	benign	-1.556	Destabilizing	0.055	N	0.375	neutral	None	None	None	None	I
V/T	0.091	likely_benign	0.0965	benign	-1.384	Destabilizing	0.002	N	0.204	neutral	None	None	None	None	I
V/W	0.7	likely_pathogenic	0.7398	pathogenic	-1.07	Destabilizing	0.958	D	0.509	neutral	None	None	None	None	I
V/Y	0.4094	ambiguous	0.4307	ambiguous	-0.757	Destabilizing	0.667	D	0.507	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.