TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19211	57856;57857;57858	chr2:178595723;178595722;178595721	chr2:179460450;179460449;179460448
N2AB	17570	52933;52934;52935	chr2:178595723;178595722;178595721	chr2:179460450;179460449;179460448
N2A	16643	50152;50153;50154	chr2:178595723;178595722;178595721	chr2:179460450;179460449;179460448
N2B	10146	30661;30662;30663	chr2:178595723;178595722;178595721	chr2:179460450;179460449;179460448
Novex-1	10271	31036;31037;31038	chr2:178595723;178595722;178595721	chr2:179460450;179460449;179460448
Novex-2	10338	31237;31238;31239	chr2:178595723;178595722;178595721	chr2:179460450;179460449;179460448
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-27
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.2979
• 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
D/V	None	None	1.0	N	0.659	0.521	0.743812340269	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
D/Y	None	None	1.0	D	0.658	0.387	0.754495299517	gnomAD-4.0.0	6.86457E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01092E-07	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
D/A	0.8288	likely_pathogenic	0.921	pathogenic	-0.212	Destabilizing	0.999	D	0.616	neutral	N	0.484334933	None	None	I
D/C	0.9506	likely_pathogenic	0.9828	pathogenic	0.148	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
D/E	0.7709	likely_pathogenic	0.8848	pathogenic	-0.674	Destabilizing	0.996	D	0.441	neutral	N	0.479700123	None	None	I
D/F	0.967	likely_pathogenic	0.9886	pathogenic	-0.513	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
D/G	0.8448	likely_pathogenic	0.9132	pathogenic	-0.464	Destabilizing	0.996	D	0.582	neutral	N	0.497212175	None	None	I
D/H	0.8345	likely_pathogenic	0.9334	pathogenic	-0.914	Destabilizing	1.0	D	0.687	prob.neutral	N	0.503199656	None	None	I
D/I	0.9391	likely_pathogenic	0.9775	pathogenic	0.412	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
D/K	0.9577	likely_pathogenic	0.9806	pathogenic	0.048	Stabilizing	0.999	D	0.619	neutral	None	None	None	None	I
D/L	0.946	likely_pathogenic	0.9738	pathogenic	0.412	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	I
D/M	0.9713	likely_pathogenic	0.9892	pathogenic	0.858	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
D/N	0.1804	likely_benign	0.2306	benign	-0.196	Destabilizing	0.884	D	0.25	neutral	N	0.492335137	None	None	I
D/P	0.9823	likely_pathogenic	0.9911	pathogenic	0.228	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
D/Q	0.9344	likely_pathogenic	0.9719	pathogenic	-0.134	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
D/R	0.9523	likely_pathogenic	0.9777	pathogenic	-0.084	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
D/S	0.5014	ambiguous	0.6569	pathogenic	-0.335	Destabilizing	0.997	D	0.589	neutral	None	None	None	None	I
D/T	0.7906	likely_pathogenic	0.8676	pathogenic	-0.134	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	I
D/V	0.8785	likely_pathogenic	0.9481	pathogenic	0.228	Stabilizing	1.0	D	0.659	neutral	N	0.499071826	None	None	I
D/W	0.9929	likely_pathogenic	0.9974	pathogenic	-0.553	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
D/Y	0.815	likely_pathogenic	0.9192	pathogenic	-0.319	Destabilizing	1.0	D	0.658	neutral	D	0.52683732	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.