TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27715	83368;83369;83370	chr2:178562989;178562988;178562987	chr2:179427716;179427715;179427714
N2AB	26074	78445;78446;78447	chr2:178562989;178562988;178562987	chr2:179427716;179427715;179427714
N2A	25147	75664;75665;75666	chr2:178562989;178562988;178562987	chr2:179427716;179427715;179427714
N2B	18650	56173;56174;56175	chr2:178562989;178562988;178562987	chr2:179427716;179427715;179427714
Novex-1	18775	56548;56549;56550	chr2:178562989;178562988;178562987	chr2:179427716;179427715;179427714
Novex-2	18842	56749;56750;56751	chr2:178562989;178562988;178562987	chr2:179427716;179427715;179427714
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-141
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.7606
• 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
I/S	None	None	0.012	N	0.283	0.196	0.585898889599	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.0996	likely_benign	0.092	benign	-0.405	Destabilizing	None	N	0.181	neutral	None	None	None	None	N
I/C	0.2995	likely_benign	0.2779	benign	-0.811	Destabilizing	0.356	N	0.326	neutral	None	None	None	None	N
I/D	0.1914	likely_benign	0.1791	benign	-0.037	Destabilizing	0.072	N	0.393	neutral	None	None	None	None	N
I/E	0.1643	likely_benign	0.1516	benign	-0.12	Destabilizing	0.072	N	0.416	neutral	None	None	None	None	N
I/F	0.1001	likely_benign	0.0996	benign	-0.55	Destabilizing	0.029	N	0.283	neutral	N	0.511297405	None	None	N
I/G	0.2011	likely_benign	0.187	benign	-0.5	Destabilizing	0.031	N	0.357	neutral	None	None	None	None	N
I/H	0.1773	likely_benign	0.1582	benign	0.096	Stabilizing	0.628	D	0.318	neutral	None	None	None	None	N
I/K	0.1132	likely_benign	0.1001	benign	-0.292	Destabilizing	0.072	N	0.418	neutral	None	None	None	None	N
I/L	0.0713	likely_benign	0.0687	benign	-0.269	Destabilizing	None	N	0.193	neutral	N	0.408343609	None	None	N
I/M	0.0702	likely_benign	0.0679	benign	-0.594	Destabilizing	0.171	N	0.314	neutral	N	0.454924048	None	None	N
I/N	0.07	likely_benign	0.0653	benign	-0.177	Destabilizing	0.055	N	0.401	neutral	N	0.384370671	None	None	N
I/P	0.1783	likely_benign	0.1492	benign	-0.287	Destabilizing	0.136	N	0.405	neutral	None	None	None	None	N
I/Q	0.1281	likely_benign	0.1152	benign	-0.315	Destabilizing	0.356	N	0.381	neutral	None	None	None	None	N
I/R	0.1116	likely_benign	0.0967	benign	0.1	Stabilizing	0.072	N	0.399	neutral	None	None	None	None	N
I/S	0.084	likely_benign	0.0741	benign	-0.583	Destabilizing	0.012	N	0.283	neutral	N	0.438453085	None	None	N
I/T	0.0834	likely_benign	0.0709	benign	-0.565	Destabilizing	None	N	0.171	neutral	N	0.393355514	None	None	N
I/V	0.0638	likely_benign	0.0616	benign	-0.287	Destabilizing	None	N	0.167	neutral	N	0.402956432	None	None	N
I/W	0.568	likely_pathogenic	0.549	ambiguous	-0.58	Destabilizing	0.864	D	0.324	neutral	None	None	None	None	N
I/Y	0.2621	likely_benign	0.2412	benign	-0.347	Destabilizing	0.356	N	0.381	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.