TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22400	67423;67424;67425	chr2:178580089;178580088;178580087	chr2:179444816;179444815;179444814
N2AB	20759	62500;62501;62502	chr2:178580089;178580088;178580087	chr2:179444816;179444815;179444814
N2A	19832	59719;59720;59721	chr2:178580089;178580088;178580087	chr2:179444816;179444815;179444814
N2B	13335	40228;40229;40230	chr2:178580089;178580088;178580087	chr2:179444816;179444815;179444814
Novex-1	13460	40603;40604;40605	chr2:178580089;178580088;178580087	chr2:179444816;179444815;179444814
Novex-2	13527	40804;40805;40806	chr2:178580089;178580088;178580087	chr2:179444816;179444815;179444814
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-50
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.591
• 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/P	rs1575883693	None	0.984	N	0.304	0.372	0.32306181527	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	2.77469E-05	None	0	0	0	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	0.0879	likely_benign	0.0813	benign	-0.483	Destabilizing	0.004	N	0.173	neutral	N	0.404985512	None	None	N
S/C	0.221	likely_benign	0.1831	benign	-0.396	Destabilizing	0.999	D	0.349	neutral	N	0.502238605	None	None	N
S/D	0.8671	likely_pathogenic	0.8811	pathogenic	0.377	Stabilizing	0.959	D	0.286	neutral	None	None	None	None	N
S/E	0.8782	likely_pathogenic	0.8863	pathogenic	0.308	Stabilizing	0.919	D	0.269	neutral	None	None	None	None	N
S/F	0.5171	ambiguous	0.5351	ambiguous	-0.952	Destabilizing	0.995	D	0.449	neutral	N	0.490882299	None	None	N
S/G	0.1788	likely_benign	0.1726	benign	-0.626	Destabilizing	0.702	D	0.353	neutral	None	None	None	None	N
S/H	0.7592	likely_pathogenic	0.7619	pathogenic	-0.973	Destabilizing	0.999	D	0.349	neutral	None	None	None	None	N
S/I	0.343	ambiguous	0.3689	ambiguous	-0.232	Destabilizing	0.976	D	0.401	neutral	None	None	None	None	N
S/K	0.9566	likely_pathogenic	0.9575	pathogenic	-0.477	Destabilizing	0.919	D	0.274	neutral	None	None	None	None	N
S/L	0.2167	likely_benign	0.211	benign	-0.232	Destabilizing	0.919	D	0.351	neutral	None	None	None	None	N
S/M	0.3434	ambiguous	0.3287	benign	-0.178	Destabilizing	0.999	D	0.347	neutral	None	None	None	None	N
S/N	0.3824	ambiguous	0.4175	ambiguous	-0.242	Destabilizing	0.959	D	0.338	neutral	None	None	None	None	N
S/P	0.6938	likely_pathogenic	0.7453	pathogenic	-0.285	Destabilizing	0.984	D	0.304	neutral	N	0.474473111	None	None	N
S/Q	0.8109	likely_pathogenic	0.8033	pathogenic	-0.423	Destabilizing	0.988	D	0.318	neutral	None	None	None	None	N
S/R	0.9353	likely_pathogenic	0.9375	pathogenic	-0.274	Destabilizing	0.988	D	0.315	neutral	None	None	None	None	N
S/T	0.1459	likely_benign	0.1458	benign	-0.363	Destabilizing	0.78	D	0.359	neutral	N	0.412431559	None	None	N
S/V	0.3032	likely_benign	0.3043	benign	-0.285	Destabilizing	0.851	D	0.348	neutral	None	None	None	None	N
S/W	0.7076	likely_pathogenic	0.7116	pathogenic	-0.951	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
S/Y	0.4361	ambiguous	0.4656	ambiguous	-0.676	Destabilizing	0.995	D	0.465	neutral	N	0.484045444	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.