TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20070	60433;60434;60435	chr2:178591611;178591610;178591609	chr2:179456338;179456337;179456336
N2AB	18429	55510;55511;55512	chr2:178591611;178591610;178591609	chr2:179456338;179456337;179456336
N2A	17502	52729;52730;52731	chr2:178591611;178591610;178591609	chr2:179456338;179456337;179456336
N2B	11005	33238;33239;33240	chr2:178591611;178591610;178591609	chr2:179456338;179456337;179456336
Novex-1	11130	33613;33614;33615	chr2:178591611;178591610;178591609	chr2:179456338;179456337;179456336
Novex-2	11197	33814;33815;33816	chr2:178591611;178591610;178591609	chr2:179456338;179456337;179456336
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-33
• Domain position: 94
• Structural Position: 131
• Q(SASA): 0.5043
• 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
Q/H	rs1204026103	None	0.998	N	0.499	0.172	0.348764635752	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
Q/A	0.3385	likely_benign	0.3017	benign	-0.265	Destabilizing	0.994	D	0.451	neutral	None	None	None	None	N
Q/C	0.6978	likely_pathogenic	0.7103	pathogenic	0.264	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
Q/D	0.6616	likely_pathogenic	0.6422	pathogenic	-0.225	Destabilizing	0.994	D	0.555	neutral	None	None	None	None	N
Q/E	0.112	likely_benign	0.1074	benign	-0.23	Destabilizing	0.982	D	0.44	neutral	N	0.467925056	None	None	N
Q/F	0.7937	likely_pathogenic	0.7902	pathogenic	-0.276	Destabilizing	0.998	D	0.739	deleterious	None	None	None	None	N
Q/G	0.4287	ambiguous	0.3952	ambiguous	-0.511	Destabilizing	0.994	D	0.512	neutral	None	None	None	None	N
Q/H	0.2743	likely_benign	0.2625	benign	-0.481	Destabilizing	0.998	D	0.499	neutral	N	0.505926084	None	None	N
Q/I	0.4352	ambiguous	0.4223	ambiguous	0.31	Stabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
Q/K	0.0859	likely_benign	0.0794	benign	-0.11	Destabilizing	0.993	D	0.401	neutral	N	0.421189902	None	None	N
Q/L	0.1988	likely_benign	0.1974	benign	0.31	Stabilizing	0.993	D	0.512	neutral	N	0.497941319	None	None	N
Q/M	0.4532	ambiguous	0.4301	ambiguous	0.651	Stabilizing	0.998	D	0.504	neutral	None	None	None	None	N
Q/N	0.48	ambiguous	0.4538	ambiguous	-0.349	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	N
Q/P	0.7273	likely_pathogenic	0.7096	pathogenic	0.148	Stabilizing	0.998	D	0.603	neutral	N	0.505926084	None	None	N
Q/R	0.0969	likely_benign	0.0902	benign	0.041	Stabilizing	0.993	D	0.54	neutral	N	0.442874683	None	None	N
Q/S	0.3933	ambiguous	0.3698	ambiguous	-0.368	Destabilizing	0.994	D	0.419	neutral	None	None	None	None	N
Q/T	0.2587	likely_benign	0.24	benign	-0.215	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
Q/V	0.2749	likely_benign	0.2609	benign	0.148	Stabilizing	0.998	D	0.521	neutral	None	None	None	None	N
Q/W	0.6857	likely_pathogenic	0.6739	pathogenic	-0.225	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
Q/Y	0.6309	likely_pathogenic	0.6193	pathogenic	-0.002	Destabilizing	0.998	D	0.526	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.