TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28525	85798;85799;85800	chr2:178560559;178560558;178560557	chr2:179425286;179425285;179425284
N2AB	26884	80875;80876;80877	chr2:178560559;178560558;178560557	chr2:179425286;179425285;179425284
N2A	25957	78094;78095;78096	chr2:178560559;178560558;178560557	chr2:179425286;179425285;179425284
N2B	19460	58603;58604;58605	chr2:178560559;178560558;178560557	chr2:179425286;179425285;179425284
Novex-1	19585	58978;58979;58980	chr2:178560559;178560558;178560557	chr2:179425286;179425285;179425284
Novex-2	19652	59179;59180;59181	chr2:178560559;178560558;178560557	chr2:179425286;179425285;179425284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-95
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0744
• 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/I	None	None	0.997	N	0.639	0.448	0.765028627367	gnomAD-4.0.0	1.59253E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-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	0.8325	likely_pathogenic	0.8056	pathogenic	-2.555	Highly Destabilizing	0.999	D	0.656	neutral	D	0.570583696	None	None	N
V/C	0.9685	likely_pathogenic	0.9688	pathogenic	-1.998	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/D	0.9962	likely_pathogenic	0.9955	pathogenic	-3.604	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
V/E	0.9889	likely_pathogenic	0.9871	pathogenic	-3.29	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.64968199	None	None	N
V/F	0.9138	likely_pathogenic	0.9026	pathogenic	-1.476	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/G	0.8894	likely_pathogenic	0.8649	pathogenic	-3.142	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.64968199	None	None	N
V/H	0.9976	likely_pathogenic	0.9971	pathogenic	-2.989	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/I	0.1105	likely_benign	0.116	benign	-0.833	Destabilizing	0.997	D	0.639	neutral	N	0.489498807	None	None	N
V/K	0.9902	likely_pathogenic	0.9879	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/L	0.747	likely_pathogenic	0.7318	pathogenic	-0.833	Destabilizing	0.997	D	0.672	neutral	D	0.548423609	None	None	N
V/M	0.7993	likely_pathogenic	0.7797	pathogenic	-1.078	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/N	0.9885	likely_pathogenic	0.9867	pathogenic	-2.886	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/P	0.9935	likely_pathogenic	0.9935	pathogenic	-1.391	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/Q	0.9887	likely_pathogenic	0.9863	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/R	0.9827	likely_pathogenic	0.978	pathogenic	-2.211	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/S	0.9615	likely_pathogenic	0.9527	pathogenic	-3.369	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/T	0.9168	likely_pathogenic	0.8991	pathogenic	-2.906	Highly Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
V/W	0.9987	likely_pathogenic	0.9984	pathogenic	-2.058	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/Y	0.9908	likely_pathogenic	0.9895	pathogenic	-1.772	Destabilizing	1.0	D	0.829	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.