TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28072	84439;84440;84441	chr2:178561918;178561917;178561916	chr2:179426645;179426644;179426643
N2AB	26431	79516;79517;79518	chr2:178561918;178561917;178561916	chr2:179426645;179426644;179426643
N2A	25504	76735;76736;76737	chr2:178561918;178561917;178561916	chr2:179426645;179426644;179426643
N2B	19007	57244;57245;57246	chr2:178561918;178561917;178561916	chr2:179426645;179426644;179426643
Novex-1	19132	57619;57620;57621	chr2:178561918;178561917;178561916	chr2:179426645;179426644;179426643
Novex-2	19199	57820;57821;57822	chr2:178561918;178561917;178561916	chr2:179426645;179426644;179426643
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-92
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0719
• 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/K	rs1475606876	-2.21	0.667	D	0.809	0.473	0.815240669409	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
I/K	rs1475606876	-2.21	0.667	D	0.809	0.473	0.815240669409	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	0	0	None	0	2.52653E-05	None	0	0	8.99514E-07	0	0
I/V	None	None	None	N	0.189	0.06	0.239901079897	gnomAD-4.0.0	2.05298E-06	None	None	None	None	N	None	0	0	None	3.82731E-05	0	None	0	0	1.79902E-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	0.5488	ambiguous	0.437	ambiguous	-2.841	Highly Destabilizing	0.072	N	0.687	prob.neutral	None	None	None	None	N
I/C	0.6587	likely_pathogenic	0.6182	pathogenic	-2.242	Highly Destabilizing	0.909	D	0.797	deleterious	None	None	None	None	N
I/D	0.9927	likely_pathogenic	0.9858	pathogenic	-3.138	Highly Destabilizing	0.726	D	0.828	deleterious	None	None	None	None	N
I/E	0.9846	likely_pathogenic	0.9723	pathogenic	-2.81	Highly Destabilizing	0.726	D	0.806	deleterious	None	None	None	None	N
I/F	0.4584	ambiguous	0.4424	ambiguous	-1.756	Destabilizing	0.567	D	0.721	prob.delet.	None	None	None	None	N
I/G	0.936	likely_pathogenic	0.8947	pathogenic	-3.46	Highly Destabilizing	0.726	D	0.785	deleterious	None	None	None	None	N
I/H	0.9766	likely_pathogenic	0.9565	pathogenic	-3.122	Highly Destabilizing	0.968	D	0.805	deleterious	None	None	None	None	N
I/K	0.9696	likely_pathogenic	0.9391	pathogenic	-1.999	Destabilizing	0.667	D	0.809	deleterious	D	0.52210406	None	None	N
I/L	0.1269	likely_benign	0.1204	benign	-0.978	Destabilizing	0.025	N	0.414	neutral	N	0.453139244	None	None	N
I/M	0.1109	likely_benign	0.115	benign	-1.295	Destabilizing	0.497	N	0.677	prob.neutral	N	0.483755727	None	None	N
I/N	0.9184	likely_pathogenic	0.859	pathogenic	-2.67	Highly Destabilizing	0.89	D	0.823	deleterious	None	None	None	None	N
I/P	0.993	likely_pathogenic	0.9868	pathogenic	-1.59	Destabilizing	0.726	D	0.831	deleterious	None	None	None	None	N
I/Q	0.9619	likely_pathogenic	0.9326	pathogenic	-2.304	Highly Destabilizing	0.89	D	0.827	deleterious	None	None	None	None	N
I/R	0.9498	likely_pathogenic	0.903	pathogenic	-2.103	Highly Destabilizing	0.667	D	0.823	deleterious	D	0.52210406	None	None	N
I/S	0.7945	likely_pathogenic	0.6966	pathogenic	-3.316	Highly Destabilizing	0.567	D	0.785	deleterious	None	None	None	None	N
I/T	0.6636	likely_pathogenic	0.5246	ambiguous	-2.811	Highly Destabilizing	0.124	N	0.765	deleterious	N	0.510076191	None	None	N
I/V	0.0581	likely_benign	0.0581	benign	-1.59	Destabilizing	None	N	0.189	neutral	N	0.385892745	None	None	N
I/W	0.9865	likely_pathogenic	0.9807	pathogenic	-2.042	Highly Destabilizing	0.968	D	0.798	deleterious	None	None	None	None	N
I/Y	0.9216	likely_pathogenic	0.8784	pathogenic	-1.866	Destabilizing	0.726	D	0.835	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.