TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14005	42238;42239;42240	chr2:178635176;178635175;178635174	chr2:179499903;179499902;179499901
N2AB	12364	37315;37316;37317	chr2:178635176;178635175;178635174	chr2:179499903;179499902;179499901
N2A	11437	34534;34535;34536	chr2:178635176;178635175;178635174	chr2:179499903;179499902;179499901
N2B	4940	15043;15044;15045	chr2:178635176;178635175;178635174	chr2:179499903;179499902;179499901
Novex-1	5065	15418;15419;15420	chr2:178635176;178635175;178635174	chr2:179499903;179499902;179499901
Novex-2	5132	15619;15620;15621	chr2:178635176;178635175;178635174	chr2:179499903;179499902;179499901
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-90
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.8573
• 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
R/S	None	None	0.524	N	0.515	0.137	0.110078149338	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43579E-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
R/A	0.8461	likely_pathogenic	0.6978	pathogenic	0.119	Stabilizing	0.745	D	0.499	neutral	None	None	None	None	N
R/C	0.6392	likely_pathogenic	0.4498	ambiguous	-0.258	Destabilizing	0.998	D	0.501	neutral	None	None	None	None	N
R/D	0.95	likely_pathogenic	0.8928	pathogenic	-0.28	Destabilizing	0.935	D	0.577	neutral	None	None	None	None	N
R/E	0.7682	likely_pathogenic	0.6	pathogenic	-0.223	Destabilizing	0.935	D	0.515	neutral	None	None	None	None	N
R/F	0.8605	likely_pathogenic	0.728	pathogenic	-0.189	Destabilizing	0.994	D	0.523	neutral	None	None	None	None	N
R/G	0.7991	likely_pathogenic	0.6182	pathogenic	-0.037	Destabilizing	0.915	D	0.593	neutral	N	0.42821208	None	None	N
R/H	0.3133	likely_benign	0.1792	benign	-0.598	Destabilizing	0.994	D	0.459	neutral	None	None	None	None	N
R/I	0.6659	likely_pathogenic	0.4486	ambiguous	0.484	Stabilizing	0.961	D	0.545	neutral	None	None	None	None	N
R/K	0.2702	likely_benign	0.1827	benign	-0.105	Destabilizing	0.688	D	0.513	neutral	N	0.428044626	None	None	N
R/L	0.5891	likely_pathogenic	0.3781	ambiguous	0.484	Stabilizing	0.876	D	0.529	neutral	None	None	None	None	N
R/M	0.7141	likely_pathogenic	0.496	ambiguous	-0.076	Destabilizing	0.991	D	0.505	neutral	N	0.428755644	None	None	N
R/N	0.9001	likely_pathogenic	0.7807	pathogenic	-0.103	Destabilizing	0.935	D	0.489	neutral	None	None	None	None	N
R/P	0.9192	likely_pathogenic	0.8607	pathogenic	0.381	Stabilizing	0.994	D	0.561	neutral	None	None	None	None	N
R/Q	0.2907	likely_benign	0.1694	benign	-0.093	Destabilizing	0.978	D	0.557	neutral	None	None	None	None	N
R/S	0.8845	likely_pathogenic	0.7311	pathogenic	-0.25	Destabilizing	0.524	D	0.515	neutral	N	0.433527427	None	None	N
R/T	0.7228	likely_pathogenic	0.4677	ambiguous	-0.077	Destabilizing	0.01	N	0.304	neutral	N	0.405135637	None	None	N
R/V	0.722	likely_pathogenic	0.5268	ambiguous	0.381	Stabilizing	0.876	D	0.575	neutral	None	None	None	None	N
R/W	0.5849	likely_pathogenic	0.3891	ambiguous	-0.394	Destabilizing	0.998	D	0.503	neutral	N	0.42980598	None	None	N
R/Y	0.7402	likely_pathogenic	0.5556	ambiguous	0.03	Stabilizing	0.994	D	0.547	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.