TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25388	76387;76388;76389	chr2:178569970;178569969;178569968	chr2:179434697;179434696;179434695
N2AB	23747	71464;71465;71466	chr2:178569970;178569969;178569968	chr2:179434697;179434696;179434695
N2A	22820	68683;68684;68685	chr2:178569970;178569969;178569968	chr2:179434697;179434696;179434695
N2B	16323	49192;49193;49194	chr2:178569970;178569969;178569968	chr2:179434697;179434696;179434695
Novex-1	16448	49567;49568;49569	chr2:178569970;178569969;178569968	chr2:179434697;179434696;179434695
Novex-2	16515	49768;49769;49770	chr2:178569970;178569969;178569968	chr2:179434697;179434696;179434695
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-72
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1077
• 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
S/R	rs1707543874	None	0.939	N	0.781	0.411	0.301455362545	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66354E-05
S/T	None	None	0.815	N	0.7	0.385	0.317958651998	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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
S/A	0.4125	ambiguous	0.4088	ambiguous	-0.762	Destabilizing	0.206	N	0.565	neutral	None	None	None	None	N
S/C	0.6875	likely_pathogenic	0.6939	pathogenic	-0.842	Destabilizing	0.994	D	0.763	deleterious	D	0.532824801	None	None	N
S/D	0.9833	likely_pathogenic	0.9872	pathogenic	-1.304	Destabilizing	0.742	D	0.709	prob.delet.	None	None	None	None	N
S/E	0.9947	likely_pathogenic	0.9948	pathogenic	-1.255	Destabilizing	0.854	D	0.719	prob.delet.	None	None	None	None	N
S/F	0.995	likely_pathogenic	0.9943	pathogenic	-0.8	Destabilizing	0.984	D	0.806	deleterious	None	None	None	None	N
S/G	0.0661	likely_benign	0.0737	benign	-1.033	Destabilizing	0.001	N	0.437	neutral	N	0.395968092	None	None	N
S/H	0.9867	likely_pathogenic	0.9871	pathogenic	-1.43	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
S/I	0.994	likely_pathogenic	0.9939	pathogenic	-0.13	Destabilizing	0.979	D	0.819	deleterious	N	0.521215006	None	None	N
S/K	0.998	likely_pathogenic	0.9983	pathogenic	-0.862	Destabilizing	0.742	D	0.726	prob.delet.	None	None	None	None	N
S/L	0.9567	likely_pathogenic	0.9482	pathogenic	-0.13	Destabilizing	0.854	D	0.795	deleterious	None	None	None	None	N
S/M	0.9776	likely_pathogenic	0.9751	pathogenic	0.035	Stabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
S/N	0.9514	likely_pathogenic	0.96	pathogenic	-1.085	Destabilizing	0.684	D	0.706	prob.neutral	D	0.531810843	None	None	N
S/P	0.99	likely_pathogenic	0.9883	pathogenic	-0.307	Destabilizing	0.984	D	0.772	deleterious	None	None	None	None	N
S/Q	0.9906	likely_pathogenic	0.9909	pathogenic	-1.234	Destabilizing	0.984	D	0.726	prob.delet.	None	None	None	None	N
S/R	0.9963	likely_pathogenic	0.9963	pathogenic	-0.741	Destabilizing	0.939	D	0.781	deleterious	N	0.509187137	None	None	N
S/T	0.718	likely_pathogenic	0.7557	pathogenic	-0.947	Destabilizing	0.815	D	0.7	prob.neutral	N	0.512692629	None	None	N
S/V	0.988	likely_pathogenic	0.9886	pathogenic	-0.307	Destabilizing	0.953	D	0.801	deleterious	None	None	None	None	N
S/W	0.9945	likely_pathogenic	0.9931	pathogenic	-0.852	Destabilizing	0.996	D	0.85	deleterious	None	None	None	None	N
S/Y	0.9911	likely_pathogenic	0.9898	pathogenic	-0.537	Destabilizing	0.984	D	0.802	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.