TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19916	59971;59972;59973	chr2:178592158;178592157;178592156	chr2:179456885;179456884;179456883
N2AB	18275	55048;55049;55050	chr2:178592158;178592157;178592156	chr2:179456885;179456884;179456883
N2A	17348	52267;52268;52269	chr2:178592158;178592157;178592156	chr2:179456885;179456884;179456883
N2B	10851	32776;32777;32778	chr2:178592158;178592157;178592156	chr2:179456885;179456884;179456883
Novex-1	10976	33151;33152;33153	chr2:178592158;178592157;178592156	chr2:179456885;179456884;179456883
Novex-2	11043	33352;33353;33354	chr2:178592158;178592157;178592156	chr2:179456885;179456884;179456883
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-32
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2443
• 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
R/K	None	None	0.002	N	0.262	0.136	0.222439326576	gnomAD-4.0.0	6.84568E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99679E-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
R/A	0.6479	likely_pathogenic	0.748	pathogenic	-2.21	Highly Destabilizing	0.688	D	0.539	neutral	None	None	None	None	N
R/C	0.2109	likely_benign	0.246	benign	-2.049	Highly Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
R/D	0.9508	likely_pathogenic	0.9716	pathogenic	-1.306	Destabilizing	0.842	D	0.64	neutral	None	None	None	None	N
R/E	0.6371	likely_pathogenic	0.743	pathogenic	-1.047	Destabilizing	0.525	D	0.557	neutral	None	None	None	None	N
R/F	0.6758	likely_pathogenic	0.765	pathogenic	-1.254	Destabilizing	0.991	D	0.687	prob.neutral	None	None	None	None	N
R/G	0.5785	likely_pathogenic	0.6764	pathogenic	-2.599	Highly Destabilizing	0.801	D	0.6	neutral	N	0.478521581	None	None	N
R/H	0.1896	likely_benign	0.2243	benign	-1.943	Destabilizing	0.991	D	0.605	neutral	None	None	None	None	N
R/I	0.3617	ambiguous	0.4655	ambiguous	-1.059	Destabilizing	0.974	D	0.673	neutral	None	None	None	None	N
R/K	0.087	likely_benign	0.0959	benign	-1.128	Destabilizing	0.002	N	0.262	neutral	N	0.412871489	None	None	N
R/L	0.342	ambiguous	0.4479	ambiguous	-1.059	Destabilizing	0.842	D	0.6	neutral	None	None	None	None	N
R/M	0.3444	ambiguous	0.4376	ambiguous	-1.509	Destabilizing	0.989	D	0.638	neutral	N	0.498412961	None	None	N
R/N	0.8661	likely_pathogenic	0.915	pathogenic	-1.618	Destabilizing	0.842	D	0.569	neutral	None	None	None	None	N
R/P	0.9826	likely_pathogenic	0.9873	pathogenic	-1.434	Destabilizing	0.974	D	0.649	neutral	None	None	None	None	N
R/Q	0.1439	likely_benign	0.1677	benign	-1.429	Destabilizing	0.842	D	0.609	neutral	None	None	None	None	N
R/S	0.7705	likely_pathogenic	0.8436	pathogenic	-2.57	Highly Destabilizing	0.801	D	0.58	neutral	N	0.465012455	None	None	N
R/T	0.5159	ambiguous	0.6321	pathogenic	-2.065	Highly Destabilizing	0.801	D	0.551	neutral	N	0.466151318	None	None	N
R/V	0.4623	ambiguous	0.5539	ambiguous	-1.434	Destabilizing	0.974	D	0.66	neutral	None	None	None	None	N
R/W	0.3038	likely_benign	0.378	ambiguous	-0.67	Destabilizing	0.997	D	0.687	prob.neutral	N	0.468251232	None	None	N
R/Y	0.512	ambiguous	0.6036	pathogenic	-0.619	Destabilizing	0.991	D	0.666	neutral	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.