TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15016	45271;45272;45273	chr2:178621876;178621875;178621874	chr2:179486603;179486602;179486601
N2AB	13375	40348;40349;40350	chr2:178621876;178621875;178621874	chr2:179486603;179486602;179486601
N2A	12448	37567;37568;37569	chr2:178621876;178621875;178621874	chr2:179486603;179486602;179486601
N2B	5951	18076;18077;18078	chr2:178621876;178621875;178621874	chr2:179486603;179486602;179486601
Novex-1	6076	18451;18452;18453	chr2:178621876;178621875;178621874	chr2:179486603;179486602;179486601
Novex-2	6143	18652;18653;18654	chr2:178621876;178621875;178621874	chr2:179486603;179486602;179486601
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-101
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.6709
• 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	0.062	N	0.563	0.142	0.234412748748	gnomAD-4.0.0	1.59483E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43427E-05	0
R/T	None	None	0.117	N	0.555	0.146	0.245101548738	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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
R/A	0.2719	likely_benign	0.288	benign	-0.018	Destabilizing	0.035	N	0.524	neutral	None	None	None	None	N
R/C	0.2625	likely_benign	0.2701	benign	-0.381	Destabilizing	0.935	D	0.549	neutral	None	None	None	None	N
R/D	0.4295	ambiguous	0.468	ambiguous	-0.4	Destabilizing	0.149	N	0.534	neutral	None	None	None	None	N
R/E	0.2699	likely_benign	0.2751	benign	-0.374	Destabilizing	0.035	N	0.481	neutral	None	None	None	None	N
R/F	0.6052	likely_pathogenic	0.6089	pathogenic	-0.398	Destabilizing	0.791	D	0.533	neutral	None	None	None	None	N
R/G	0.1415	likely_benign	0.1497	benign	-0.12	Destabilizing	0.117	N	0.568	neutral	N	0.402361062	None	None	N
R/H	0.1549	likely_benign	0.1548	benign	-0.614	Destabilizing	0.555	D	0.521	neutral	None	None	None	None	N
R/I	0.3091	likely_benign	0.2998	benign	0.2	Stabilizing	0.555	D	0.537	neutral	None	None	None	None	N
R/K	0.1045	likely_benign	0.1079	benign	-0.306	Destabilizing	None	N	0.199	neutral	N	0.415263212	None	None	N
R/L	0.2353	likely_benign	0.2396	benign	0.2	Stabilizing	0.149	N	0.568	neutral	None	None	None	None	N
R/M	0.2763	likely_benign	0.2775	benign	-0.209	Destabilizing	0.741	D	0.518	neutral	N	0.441157988	None	None	N
R/N	0.3898	ambiguous	0.4269	ambiguous	-0.278	Destabilizing	0.149	N	0.511	neutral	None	None	None	None	N
R/P	0.2994	likely_benign	0.3228	benign	0.142	Stabilizing	0.555	D	0.541	neutral	None	None	None	None	N
R/Q	0.1046	likely_benign	0.1076	benign	-0.276	Destabilizing	0.081	N	0.544	neutral	None	None	None	None	N
R/S	0.3295	likely_benign	0.3454	ambiguous	-0.386	Destabilizing	0.062	N	0.563	neutral	N	0.439349723	None	None	N
R/T	0.2147	likely_benign	0.2163	benign	-0.273	Destabilizing	0.117	N	0.555	neutral	N	0.440724558	None	None	N
R/V	0.368	ambiguous	0.3743	ambiguous	0.142	Stabilizing	0.38	N	0.528	neutral	None	None	None	None	N
R/W	0.281	likely_benign	0.2656	benign	-0.639	Destabilizing	0.915	D	0.591	neutral	N	0.511712952	None	None	N
R/Y	0.4827	ambiguous	0.4903	ambiguous	-0.248	Destabilizing	0.555	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.