TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16813	50662;50663;50664	chr2:178611872;178611871;178611870	chr2:179476599;179476598;179476597
N2AB	15172	45739;45740;45741	chr2:178611872;178611871;178611870	chr2:179476599;179476598;179476597
N2A	14245	42958;42959;42960	chr2:178611872;178611871;178611870	chr2:179476599;179476598;179476597
N2B	7748	23467;23468;23469	chr2:178611872;178611871;178611870	chr2:179476599;179476598;179476597
Novex-1	7873	23842;23843;23844	chr2:178611872;178611871;178611870	chr2:179476599;179476598;179476597
Novex-2	7940	24043;24044;24045	chr2:178611872;178611871;178611870	chr2:179476599;179476598;179476597
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: Fn3-10
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1223
• 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	0.538	0.281	0.618934792644	gnomAD-4.0.0	1.36912E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99802E-07	0	1.65777E-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
V/A	0.9106	likely_pathogenic	0.9293	pathogenic	-1.933	Destabilizing	0.999	D	0.635	neutral	D	0.531670492	None	None	N
V/C	0.9651	likely_pathogenic	0.9635	pathogenic	-1.424	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/D	0.9958	likely_pathogenic	0.9979	pathogenic	-2.779	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/E	0.9841	likely_pathogenic	0.9905	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.827	deleterious	D	0.721360654	None	None	N
V/F	0.8618	likely_pathogenic	0.8662	pathogenic	-1.138	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/G	0.9545	likely_pathogenic	0.9726	pathogenic	-2.53	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.721360654	None	None	N
V/H	0.9957	likely_pathogenic	0.9971	pathogenic	-2.431	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/I	0.1482	likely_benign	0.1335	benign	-0.232	Destabilizing	0.997	D	0.538	neutral	N	0.483417631	None	None	N
V/K	0.9895	likely_pathogenic	0.994	pathogenic	-1.634	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/L	0.6993	likely_pathogenic	0.6795	pathogenic	-0.232	Destabilizing	0.997	D	0.651	neutral	N	0.473152362	None	None	N
V/M	0.7175	likely_pathogenic	0.6636	pathogenic	-0.33	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/N	0.9885	likely_pathogenic	0.9927	pathogenic	-2.177	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/P	0.9943	likely_pathogenic	0.9964	pathogenic	-0.774	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/Q	0.9849	likely_pathogenic	0.9901	pathogenic	-1.886	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/R	0.985	likely_pathogenic	0.9916	pathogenic	-1.704	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/S	0.9754	likely_pathogenic	0.9844	pathogenic	-2.759	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/T	0.9549	likely_pathogenic	0.965	pathogenic	-2.303	Highly Destabilizing	0.999	D	0.606	neutral	None	None	None	None	N
V/W	0.9973	likely_pathogenic	0.9979	pathogenic	-1.725	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Y	0.985	likely_pathogenic	0.9887	pathogenic	-1.273	Destabilizing	1.0	D	0.797	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.