TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29828	89707;89708;89709	chr2:178553523;178553522;178553521	chr2:179418250;179418249;179418248
N2AB	28187	84784;84785;84786	chr2:178553523;178553522;178553521	chr2:179418250;179418249;179418248
N2A	27260	82003;82004;82005	chr2:178553523;178553522;178553521	chr2:179418250;179418249;179418248
N2B	20763	62512;62513;62514	chr2:178553523;178553522;178553521	chr2:179418250;179418249;179418248
Novex-1	20888	62887;62888;62889	chr2:178553523;178553522;178553521	chr2:179418250;179418249;179418248
Novex-2	20955	63088;63089;63090	chr2:178553523;178553522;178553521	chr2:179418250;179418249;179418248
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: Fn3-105
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.1768
• 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/I	None	None	None	N	0.325	0.14	0.297718772494	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.1378	likely_benign	0.1149	benign	-1.749	Destabilizing	None	N	0.323	neutral	N	0.491003522	None	None	N
V/C	0.6014	likely_pathogenic	0.5642	pathogenic	-1.118	Destabilizing	0.823	D	0.707	prob.delet.	None	None	None	None	N
V/D	0.6041	likely_pathogenic	0.526	ambiguous	-2.277	Highly Destabilizing	0.378	N	0.878	deleterious	None	None	None	None	N
V/E	0.3761	ambiguous	0.3412	ambiguous	-2.049	Highly Destabilizing	0.314	N	0.779	deleterious	N	0.507248126	None	None	N
V/F	0.1972	likely_benign	0.1787	benign	-1.057	Destabilizing	0.378	N	0.741	deleterious	None	None	None	None	N
V/G	0.267	likely_benign	0.232	benign	-2.265	Highly Destabilizing	0.061	N	0.764	deleterious	N	0.519275995	None	None	N
V/H	0.5632	ambiguous	0.521	ambiguous	-1.888	Destabilizing	0.934	D	0.843	deleterious	None	None	None	None	N
V/I	0.0916	likely_benign	0.0863	benign	-0.313	Destabilizing	None	N	0.325	neutral	N	0.495428584	None	None	N
V/K	0.3735	ambiguous	0.3572	ambiguous	-1.394	Destabilizing	0.378	N	0.787	deleterious	None	None	None	None	N
V/L	0.2281	likely_benign	0.2049	benign	-0.313	Destabilizing	0.026	N	0.569	neutral	N	0.47571997	None	None	N
V/M	0.18	likely_benign	0.1604	benign	-0.304	Destabilizing	0.378	N	0.659	prob.neutral	None	None	None	None	N
V/N	0.4188	ambiguous	0.3738	ambiguous	-1.765	Destabilizing	0.552	D	0.875	deleterious	None	None	None	None	N
V/P	0.8557	likely_pathogenic	0.7904	pathogenic	-0.766	Destabilizing	0.378	N	0.813	deleterious	None	None	None	None	N
V/Q	0.3017	likely_benign	0.2879	benign	-1.603	Destabilizing	0.552	D	0.807	deleterious	None	None	None	None	N
V/R	0.3168	likely_benign	0.3165	benign	-1.288	Destabilizing	0.378	N	0.878	deleterious	None	None	None	None	N
V/S	0.2208	likely_benign	0.1997	benign	-2.352	Highly Destabilizing	0.08	N	0.731	deleterious	None	None	None	None	N
V/T	0.1716	likely_benign	0.1466	benign	-1.972	Destabilizing	0.08	N	0.604	neutral	None	None	None	None	N
V/W	0.8515	likely_pathogenic	0.8035	pathogenic	-1.52	Destabilizing	0.934	D	0.787	deleterious	None	None	None	None	N
V/Y	0.5336	ambiguous	0.4693	ambiguous	-1.078	Destabilizing	0.552	D	0.721	deleterious	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.