TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25457	76594;76595;76596	chr2:178569763;178569762;178569761	chr2:179434490;179434489;179434488
N2AB	23816	71671;71672;71673	chr2:178569763;178569762;178569761	chr2:179434490;179434489;179434488
N2A	22889	68890;68891;68892	chr2:178569763;178569762;178569761	chr2:179434490;179434489;179434488
N2B	16392	49399;49400;49401	chr2:178569763;178569762;178569761	chr2:179434490;179434489;179434488
Novex-1	16517	49774;49775;49776	chr2:178569763;178569762;178569761	chr2:179434490;179434489;179434488
Novex-2	16584	49975;49976;49977	chr2:178569763;178569762;178569761	chr2:179434490;179434489;179434488
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-73
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6543
• 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
P/S	None	None	0.414	N	0.334	0.366	0.327686398923	gnomAD-4.0.0	1.59254E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85927E-06	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
P/A	0.1092	likely_benign	0.1112	benign	-0.846	Destabilizing	0.919	D	0.527	neutral	N	0.48318251	None	None	N
P/C	0.5691	likely_pathogenic	0.5858	pathogenic	-0.625	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
P/D	0.5163	ambiguous	0.5302	ambiguous	-0.499	Destabilizing	0.991	D	0.641	neutral	None	None	None	None	N
P/E	0.3328	likely_benign	0.324	benign	-0.582	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	N
P/F	0.4861	ambiguous	0.4935	ambiguous	-0.863	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
P/G	0.389	ambiguous	0.4097	ambiguous	-1.046	Destabilizing	0.938	D	0.608	neutral	None	None	None	None	N
P/H	0.2422	likely_benign	0.234	benign	-0.565	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
P/I	0.3331	likely_benign	0.3351	benign	-0.446	Destabilizing	0.995	D	0.712	prob.delet.	None	None	None	None	N
P/K	0.3009	likely_benign	0.2943	benign	-0.684	Destabilizing	0.991	D	0.643	neutral	None	None	None	None	N
P/L	0.1195	likely_benign	0.1203	benign	-0.446	Destabilizing	0.988	D	0.683	prob.neutral	N	0.476722199	None	None	N
P/M	0.3082	likely_benign	0.3128	benign	-0.363	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
P/N	0.3765	ambiguous	0.3915	ambiguous	-0.393	Destabilizing	0.991	D	0.669	neutral	None	None	None	None	N
P/Q	0.1821	likely_benign	0.1829	benign	-0.629	Destabilizing	0.988	D	0.695	prob.neutral	D	0.524298414	None	None	N
P/R	0.2468	likely_benign	0.2358	benign	-0.13	Destabilizing	0.988	D	0.686	prob.neutral	N	0.50605937	None	None	N
P/S	0.1399	likely_benign	0.1492	benign	-0.818	Destabilizing	0.414	N	0.334	neutral	N	0.483355869	None	None	N
P/T	0.1397	likely_benign	0.1396	benign	-0.797	Destabilizing	0.976	D	0.655	neutral	N	0.462961954	None	None	N
P/V	0.2396	likely_benign	0.2362	benign	-0.543	Destabilizing	0.991	D	0.671	neutral	None	None	None	None	N
P/W	0.7312	likely_pathogenic	0.7197	pathogenic	-0.959	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/Y	0.4603	ambiguous	0.4541	ambiguous	-0.672	Destabilizing	1.0	D	0.696	prob.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.