TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27003	81232;81233;81234	chr2:178565125;178565124;178565123	chr2:179429852;179429851;179429850
N2AB	25362	76309;76310;76311	chr2:178565125;178565124;178565123	chr2:179429852;179429851;179429850
N2A	24435	73528;73529;73530	chr2:178565125;178565124;178565123	chr2:179429852;179429851;179429850
N2B	17938	54037;54038;54039	chr2:178565125;178565124;178565123	chr2:179429852;179429851;179429850
Novex-1	18063	54412;54413;54414	chr2:178565125;178565124;178565123	chr2:179429852;179429851;179429850
Novex-2	18130	54613;54614;54615	chr2:178565125;178565124;178565123	chr2:179429852;179429851;179429850
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-84
• Domain position: 32
• Structural Position: 33
• Q(SASA): 0.171
• Predicted PPI site: I

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
C/Y	rs1359547274	-1.298	0.99	N	0.666	0.513	0.739085393083	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	9.98E-05	0	None	0	None	0	0	0
C/Y	rs1359547274	-1.298	0.99	N	0.666	0.513	0.739085393083	gnomAD-4.0.0	1.59216E-06	None	None	None	None	I	None	0	0	None	4.7719E-05	0	None	0	0	0	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
C/A	0.7212	likely_pathogenic	0.6438	pathogenic	-1.739	Destabilizing	0.559	D	0.563	neutral	None	None	None	None	I
C/D	0.9843	likely_pathogenic	0.9787	pathogenic	-0.103	Destabilizing	0.956	D	0.697	prob.neutral	None	None	None	None	I
C/E	0.9925	likely_pathogenic	0.9902	pathogenic	-0.044	Destabilizing	0.956	D	0.701	prob.neutral	None	None	None	None	I
C/F	0.7194	likely_pathogenic	0.6732	pathogenic	-1.247	Destabilizing	0.97	D	0.663	neutral	N	0.477431944	None	None	I
C/G	0.5013	ambiguous	0.4401	ambiguous	-2.003	Highly Destabilizing	0.698	D	0.656	neutral	N	0.462734588	None	None	I
C/H	0.9553	likely_pathogenic	0.9441	pathogenic	-1.945	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	I
C/I	0.874	likely_pathogenic	0.8432	pathogenic	-1.075	Destabilizing	0.978	D	0.605	neutral	None	None	None	None	I
C/K	0.9952	likely_pathogenic	0.9937	pathogenic	-0.803	Destabilizing	0.956	D	0.693	prob.neutral	None	None	None	None	I
C/L	0.8778	likely_pathogenic	0.8481	pathogenic	-1.075	Destabilizing	0.86	D	0.565	neutral	None	None	None	None	I
C/M	0.8839	likely_pathogenic	0.8531	pathogenic	-0.237	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	I
C/N	0.8721	likely_pathogenic	0.8401	pathogenic	-0.614	Destabilizing	0.956	D	0.703	prob.neutral	None	None	None	None	I
C/P	0.9963	likely_pathogenic	0.9953	pathogenic	-1.272	Destabilizing	0.978	D	0.697	prob.neutral	None	None	None	None	I
C/Q	0.9695	likely_pathogenic	0.9599	pathogenic	-0.63	Destabilizing	0.956	D	0.708	prob.delet.	None	None	None	None	I
C/R	0.9673	likely_pathogenic	0.9602	pathogenic	-0.561	Destabilizing	0.942	D	0.696	prob.neutral	N	0.516822576	None	None	I
C/S	0.4527	ambiguous	0.3874	ambiguous	-1.199	Destabilizing	0.058	N	0.463	neutral	N	0.401574273	None	None	I
C/T	0.7328	likely_pathogenic	0.6978	pathogenic	-0.969	Destabilizing	0.754	D	0.573	neutral	None	None	None	None	I
C/V	0.7392	likely_pathogenic	0.6922	pathogenic	-1.272	Destabilizing	0.86	D	0.597	neutral	None	None	None	None	I
C/W	0.9432	likely_pathogenic	0.9273	pathogenic	-1.143	Destabilizing	0.997	D	0.689	prob.neutral	N	0.50392999	None	None	I
C/Y	0.8936	likely_pathogenic	0.8635	pathogenic	-1.155	Destabilizing	0.99	D	0.666	neutral	N	0.485572246	None	None	I

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.