TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2460	7603;7604;7605	chr2:178773678;178773677;178773676	chr2:179638405;179638404;179638403
N2AB	2460	7603;7604;7605	chr2:178773678;178773677;178773676	chr2:179638405;179638404;179638403
N2A	2460	7603;7604;7605	chr2:178773678;178773677;178773676	chr2:179638405;179638404;179638403
N2B	2414	7465;7466;7467	chr2:178773678;178773677;178773676	chr2:179638405;179638404;179638403
Novex-1	2414	7465;7466;7467	chr2:178773678;178773677;178773676	chr2:179638405;179638404;179638403
Novex-2	2414	7465;7466;7467	chr2:178773678;178773677;178773676	chr2:179638405;179638404;179638403
Novex-3	2460	7603;7604;7605	chr2:178773678;178773677;178773676	chr2:179638405;179638404;179638403

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-14
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.285
• 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
T/A	None	None	0.919	N	0.42	0.199	0.195762928549	gnomAD-4.0.0	1.59071E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85673E-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
T/A	0.1571	likely_benign	0.1548	benign	-0.733	Destabilizing	0.919	D	0.42	neutral	N	0.448707792	None	None	N
T/C	0.653	likely_pathogenic	0.6484	pathogenic	-0.412	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
T/D	0.5868	likely_pathogenic	0.5873	pathogenic	0.315	Stabilizing	0.995	D	0.589	neutral	None	None	None	None	N
T/E	0.4204	ambiguous	0.4211	ambiguous	0.273	Stabilizing	0.991	D	0.594	neutral	None	None	None	None	N
T/F	0.5974	likely_pathogenic	0.5827	pathogenic	-1.012	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
T/G	0.3675	ambiguous	0.3688	ambiguous	-0.92	Destabilizing	0.991	D	0.601	neutral	None	None	None	None	N
T/H	0.4991	ambiguous	0.5022	ambiguous	-1.216	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
T/I	0.5272	ambiguous	0.5077	ambiguous	-0.344	Destabilizing	0.994	D	0.643	neutral	N	0.512221962	None	None	N
T/K	0.2736	likely_benign	0.2681	benign	-0.472	Destabilizing	0.991	D	0.593	neutral	None	None	None	None	N
T/L	0.2652	likely_benign	0.2531	benign	-0.344	Destabilizing	0.968	D	0.522	neutral	None	None	None	None	N
T/M	0.1512	likely_benign	0.1506	benign	-0.045	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
T/N	0.1935	likely_benign	0.1909	benign	-0.291	Destabilizing	0.994	D	0.659	neutral	N	0.443763509	None	None	N
T/P	0.7064	likely_pathogenic	0.7112	pathogenic	-0.444	Destabilizing	0.067	N	0.331	neutral	D	0.550308438	None	None	N
T/Q	0.294	likely_benign	0.2969	benign	-0.524	Destabilizing	0.995	D	0.669	neutral	None	None	None	None	N
T/R	0.2393	likely_benign	0.2375	benign	-0.24	Destabilizing	0.995	D	0.643	neutral	None	None	None	None	N
T/S	0.1636	likely_benign	0.1629	benign	-0.632	Destabilizing	0.958	D	0.423	neutral	N	0.44029738	None	None	N
T/V	0.3688	ambiguous	0.3502	ambiguous	-0.444	Destabilizing	0.984	D	0.494	neutral	None	None	None	None	N
T/W	0.8555	likely_pathogenic	0.8565	pathogenic	-0.908	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/Y	0.6153	likely_pathogenic	0.6113	pathogenic	-0.674	Destabilizing	0.998	D	0.707	prob.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.