TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22697	68314;68315;68316	chr2:178578941;178578940;178578939	chr2:179443668;179443667;179443666
N2AB	21056	63391;63392;63393	chr2:178578941;178578940;178578939	chr2:179443668;179443667;179443666
N2A	20129	60610;60611;60612	chr2:178578941;178578940;178578939	chr2:179443668;179443667;179443666
N2B	13632	41119;41120;41121	chr2:178578941;178578940;178578939	chr2:179443668;179443667;179443666
Novex-1	13757	41494;41495;41496	chr2:178578941;178578940;178578939	chr2:179443668;179443667;179443666
Novex-2	13824	41695;41696;41697	chr2:178578941;178578940;178578939	chr2:179443668;179443667;179443666
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-52
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.5713
• 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
A/P	None	None	0.994	N	0.749	0.412	0.498194598333	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
A/V	None	None	0.979	N	0.613	0.303	0.493295820912	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
A/C	0.6678	likely_pathogenic	0.6734	pathogenic	-0.766	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
A/D	0.879	likely_pathogenic	0.8622	pathogenic	-0.494	Destabilizing	0.976	D	0.687	prob.neutral	N	0.466588544	None	None	N
A/E	0.8371	likely_pathogenic	0.8319	pathogenic	-0.644	Destabilizing	0.18	N	0.321	neutral	None	None	None	None	N
A/F	0.7349	likely_pathogenic	0.7206	pathogenic	-0.916	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
A/G	0.3029	likely_benign	0.2824	benign	-0.424	Destabilizing	0.958	D	0.523	neutral	N	0.446792062	None	None	N
A/H	0.8507	likely_pathogenic	0.8482	pathogenic	-0.432	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
A/I	0.6873	likely_pathogenic	0.685	pathogenic	-0.369	Destabilizing	0.995	D	0.749	deleterious	None	None	None	None	N
A/K	0.9387	likely_pathogenic	0.9347	pathogenic	-0.689	Destabilizing	0.982	D	0.724	prob.delet.	None	None	None	None	N
A/L	0.4475	ambiguous	0.4441	ambiguous	-0.369	Destabilizing	0.968	D	0.7	prob.neutral	None	None	None	None	N
A/M	0.4786	ambiguous	0.4638	ambiguous	-0.379	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
A/N	0.596	likely_pathogenic	0.58	pathogenic	-0.354	Destabilizing	0.991	D	0.732	prob.delet.	None	None	None	None	N
A/P	0.8834	likely_pathogenic	0.8769	pathogenic	-0.33	Destabilizing	0.994	D	0.749	deleterious	N	0.461545297	None	None	N
A/Q	0.758	likely_pathogenic	0.7625	pathogenic	-0.645	Destabilizing	0.982	D	0.749	deleterious	None	None	None	None	N
A/R	0.8762	likely_pathogenic	0.8743	pathogenic	-0.201	Destabilizing	0.991	D	0.748	deleterious	None	None	None	None	N
A/S	0.134	likely_benign	0.1328	benign	-0.575	Destabilizing	0.958	D	0.457	neutral	N	0.436188279	None	None	N
A/T	0.1975	likely_benign	0.1819	benign	-0.645	Destabilizing	0.988	D	0.692	prob.neutral	N	0.436575068	None	None	N
A/V	0.3684	ambiguous	0.3631	ambiguous	-0.33	Destabilizing	0.979	D	0.613	neutral	N	0.461876158	None	None	N
A/W	0.9564	likely_pathogenic	0.9567	pathogenic	-1.052	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
A/Y	0.8477	likely_pathogenic	0.8328	pathogenic	-0.705	Destabilizing	1.0	D	0.749	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.