TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23333	70222;70223;70224	chr2:178576135;178576134;178576133	chr2:179440862;179440861;179440860
N2AB	21692	65299;65300;65301	chr2:178576135;178576134;178576133	chr2:179440862;179440861;179440860
N2A	20765	62518;62519;62520	chr2:178576135;178576134;178576133	chr2:179440862;179440861;179440860
N2B	14268	43027;43028;43029	chr2:178576135;178576134;178576133	chr2:179440862;179440861;179440860
Novex-1	14393	43402;43403;43404	chr2:178576135;178576134;178576133	chr2:179440862;179440861;179440860
Novex-2	14460	43603;43604;43605	chr2:178576135;178576134;178576133	chr2:179440862;179440861;179440860
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-57
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.318
• 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
V/A	None	None	0.982	N	0.426	0.311	0.661867001231	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
V/F	rs1710003146	None	0.995	N	0.777	0.299	0.675861982728	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
V/A	0.2024	likely_benign	0.2058	benign	-2.021	Highly Destabilizing	0.982	D	0.426	neutral	N	0.489881983	None	None	N
V/C	0.7409	likely_pathogenic	0.7475	pathogenic	-1.341	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
V/D	0.6961	likely_pathogenic	0.7129	pathogenic	-2.714	Highly Destabilizing	0.999	D	0.83	deleterious	N	0.510201327	None	None	N
V/E	0.5114	ambiguous	0.5293	ambiguous	-2.529	Highly Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
V/F	0.33	likely_benign	0.3416	ambiguous	-1.318	Destabilizing	0.995	D	0.777	deleterious	N	0.509681252	None	None	N
V/G	0.4461	ambiguous	0.4508	ambiguous	-2.519	Highly Destabilizing	0.999	D	0.821	deleterious	N	0.510027969	None	None	N
V/H	0.7517	likely_pathogenic	0.7696	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/I	0.0809	likely_benign	0.0842	benign	-0.643	Destabilizing	0.429	N	0.252	neutral	N	0.4860681	None	None	N
V/K	0.5095	ambiguous	0.5386	ambiguous	-1.782	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/L	0.3475	ambiguous	0.3446	ambiguous	-0.643	Destabilizing	0.921	D	0.412	neutral	N	0.4881484	None	None	N
V/M	0.1738	likely_benign	0.182	benign	-0.463	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
V/N	0.535	ambiguous	0.5549	ambiguous	-1.994	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
V/P	0.9089	likely_pathogenic	0.9096	pathogenic	-1.075	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
V/Q	0.5052	ambiguous	0.5225	ambiguous	-1.913	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/R	0.4874	ambiguous	0.5124	ambiguous	-1.499	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/S	0.3721	ambiguous	0.3813	ambiguous	-2.541	Highly Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
V/T	0.142	likely_benign	0.1414	benign	-2.224	Highly Destabilizing	0.993	D	0.677	prob.neutral	None	None	None	None	N
V/W	0.9119	likely_pathogenic	0.9169	pathogenic	-1.861	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/Y	0.7245	likely_pathogenic	0.7423	pathogenic	-1.457	Destabilizing	0.999	D	0.785	deleterious	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.