TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26246	78961;78962;78963	chr2:178567396;178567395;178567394	chr2:179432123;179432122;179432121
N2AB	24605	74038;74039;74040	chr2:178567396;178567395;178567394	chr2:179432123;179432122;179432121
N2A	23678	71257;71258;71259	chr2:178567396;178567395;178567394	chr2:179432123;179432122;179432121
N2B	17181	51766;51767;51768	chr2:178567396;178567395;178567394	chr2:179432123;179432122;179432121
Novex-1	17306	52141;52142;52143	chr2:178567396;178567395;178567394	chr2:179432123;179432122;179432121
Novex-2	17373	52342;52343;52344	chr2:178567396;178567395;178567394	chr2:179432123;179432122;179432121
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: Ig-137
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.5252
• 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
D/N	rs866667558	None	0.978	N	0.59	0.345	0.231231049324	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
D/A	0.2051	likely_benign	0.2246	benign	-0.091	Destabilizing	0.957	D	0.607	neutral	N	0.468720714	None	None	N
D/C	0.7767	likely_pathogenic	0.777	pathogenic	-0.176	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
D/E	0.2432	likely_benign	0.2615	benign	-0.247	Destabilizing	0.039	N	0.245	neutral	N	0.451804547	None	None	N
D/F	0.8037	likely_pathogenic	0.7954	pathogenic	0.17	Stabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
D/G	0.2811	likely_benign	0.3025	benign	-0.298	Destabilizing	0.928	D	0.609	neutral	N	0.500687183	None	None	N
D/H	0.4673	ambiguous	0.4883	ambiguous	0.615	Stabilizing	0.997	D	0.645	neutral	N	0.460593639	None	None	N
D/I	0.4776	ambiguous	0.4527	ambiguous	0.409	Stabilizing	0.992	D	0.708	prob.delet.	None	None	None	None	N
D/K	0.5651	likely_pathogenic	0.5651	pathogenic	0.414	Stabilizing	0.968	D	0.623	neutral	None	None	None	None	N
D/L	0.4966	ambiguous	0.5007	ambiguous	0.409	Stabilizing	0.983	D	0.669	neutral	None	None	None	None	N
D/M	0.7391	likely_pathogenic	0.7311	pathogenic	0.246	Stabilizing	0.999	D	0.67	neutral	None	None	None	None	N
D/N	0.1325	likely_benign	0.135	benign	-0.114	Destabilizing	0.978	D	0.59	neutral	N	0.455438625	None	None	N
D/P	0.5288	ambiguous	0.5589	ambiguous	0.265	Stabilizing	0.992	D	0.645	neutral	None	None	None	None	N
D/Q	0.5084	ambiguous	0.5351	ambiguous	-0.03	Destabilizing	0.968	D	0.64	neutral	None	None	None	None	N
D/R	0.5788	likely_pathogenic	0.591	pathogenic	0.728	Stabilizing	0.983	D	0.67	neutral	None	None	None	None	N
D/S	0.1837	likely_benign	0.1975	benign	-0.187	Destabilizing	0.895	D	0.535	neutral	None	None	None	None	N
D/T	0.341	ambiguous	0.3432	ambiguous	-0.005	Destabilizing	0.983	D	0.659	neutral	None	None	None	None	N
D/V	0.3007	likely_benign	0.2909	benign	0.265	Stabilizing	0.978	D	0.671	neutral	N	0.483977813	None	None	N
D/W	0.9512	likely_pathogenic	0.9491	pathogenic	0.325	Stabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
D/Y	0.3652	ambiguous	0.3611	ambiguous	0.428	Stabilizing	0.999	D	0.684	prob.neutral	N	0.490561179	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.