TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19541	58846;58847;58848	chr2:178593679;178593678;178593677	chr2:179458406;179458405;179458404
N2AB	17900	53923;53924;53925	chr2:178593679;178593678;178593677	chr2:179458406;179458405;179458404
N2A	16973	51142;51143;51144	chr2:178593679;178593678;178593677	chr2:179458406;179458405;179458404
N2B	10476	31651;31652;31653	chr2:178593679;178593678;178593677	chr2:179458406;179458405;179458404
Novex-1	10601	32026;32027;32028	chr2:178593679;178593678;178593677	chr2:179458406;179458405;179458404
Novex-2	10668	32227;32228;32229	chr2:178593679;178593678;178593677	chr2:179458406;179458405;179458404
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: Fn3-29
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1196
• 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	rs760841948	-2.293	0.025	N	0.373	0.211	0.427596317008	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs760841948	-2.293	0.025	N	0.373	0.211	0.427596317008	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.6485	likely_pathogenic	0.4498	ambiguous	-1.959	Destabilizing	0.025	N	0.373	neutral	N	0.482442964	None	None	N
V/C	0.9174	likely_pathogenic	0.8645	pathogenic	-1.429	Destabilizing	0.997	D	0.743	deleterious	None	None	None	None	N
V/D	0.9854	likely_pathogenic	0.9697	pathogenic	-2.445	Highly Destabilizing	0.983	D	0.85	deleterious	N	0.497913873	None	None	N
V/E	0.9676	likely_pathogenic	0.9413	pathogenic	-2.244	Highly Destabilizing	0.975	D	0.821	deleterious	None	None	None	None	N
V/F	0.582	likely_pathogenic	0.4508	ambiguous	-1.197	Destabilizing	0.967	D	0.756	deleterious	N	0.492238652	None	None	N
V/G	0.8378	likely_pathogenic	0.7296	pathogenic	-2.474	Highly Destabilizing	0.935	D	0.807	deleterious	D	0.539655791	None	None	N
V/H	0.9871	likely_pathogenic	0.9751	pathogenic	-2.146	Highly Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
V/I	0.0955	likely_benign	0.0944	benign	-0.539	Destabilizing	0.025	N	0.272	neutral	N	0.49329793	None	None	N
V/K	0.9843	likely_pathogenic	0.9725	pathogenic	-1.801	Destabilizing	0.975	D	0.82	deleterious	None	None	None	None	N
V/L	0.5675	likely_pathogenic	0.4815	ambiguous	-0.539	Destabilizing	0.63	D	0.621	neutral	N	0.466049186	None	None	N
V/M	0.5584	ambiguous	0.4609	ambiguous	-0.478	Destabilizing	0.975	D	0.707	prob.neutral	None	None	None	None	N
V/N	0.9532	likely_pathogenic	0.9135	pathogenic	-2.053	Highly Destabilizing	0.987	D	0.849	deleterious	None	None	None	None	N
V/P	0.969	likely_pathogenic	0.9472	pathogenic	-0.983	Destabilizing	0.987	D	0.823	deleterious	None	None	None	None	N
V/Q	0.9705	likely_pathogenic	0.9473	pathogenic	-1.929	Destabilizing	0.987	D	0.833	deleterious	None	None	None	None	N
V/R	0.974	likely_pathogenic	0.9562	pathogenic	-1.567	Destabilizing	0.987	D	0.841	deleterious	None	None	None	None	N
V/S	0.8741	likely_pathogenic	0.764	pathogenic	-2.651	Highly Destabilizing	0.95	D	0.801	deleterious	None	None	None	None	N
V/T	0.7921	likely_pathogenic	0.6646	pathogenic	-2.303	Highly Destabilizing	0.916	D	0.661	neutral	None	None	None	None	N
V/W	0.991	likely_pathogenic	0.9814	pathogenic	-1.674	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/Y	0.9396	likely_pathogenic	0.8942	pathogenic	-1.275	Destabilizing	0.996	D	0.739	prob.delet.	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.