TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30581	91966;91967;91968	chr2:178550097;178550096;178550095	chr2:179414824;179414823;179414822
N2AB	28940	87043;87044;87045	chr2:178550097;178550096;178550095	chr2:179414824;179414823;179414822
N2A	28013	84262;84263;84264	chr2:178550097;178550096;178550095	chr2:179414824;179414823;179414822
N2B	21516	64771;64772;64773	chr2:178550097;178550096;178550095	chr2:179414824;179414823;179414822
Novex-1	21641	65146;65147;65148	chr2:178550097;178550096;178550095	chr2:179414824;179414823;179414822
Novex-2	21708	65347;65348;65349	chr2:178550097;178550096;178550095	chr2:179414824;179414823;179414822
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: Ig-149
• Domain position: 50
• Structural Position: 135
• Q(SASA): 0.2033
• Predicted PPI site: I

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/F	None	None	0.002	N	0.381	0.211	0.568643509186	gnomAD-4.0.0	1.59126E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8583E-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	0.1021	likely_benign	0.1013	benign	-0.596	Destabilizing	0.003	N	0.147	neutral	N	0.502120562	None	None	I
S/C	0.1101	likely_benign	0.0946	benign	-0.376	Destabilizing	0.978	D	0.504	neutral	N	0.494887945	None	None	I
S/D	0.6842	likely_pathogenic	0.6428	pathogenic	0.046	Stabilizing	0.593	D	0.393	neutral	None	None	None	None	I
S/E	0.6826	likely_pathogenic	0.6316	pathogenic	-0.019	Destabilizing	0.593	D	0.385	neutral	None	None	None	None	I
S/F	0.1863	likely_benign	0.1681	benign	-1.06	Destabilizing	0.002	N	0.381	neutral	N	0.470106931	None	None	I
S/G	0.1528	likely_benign	0.1456	benign	-0.754	Destabilizing	0.228	N	0.357	neutral	None	None	None	None	I
S/H	0.4323	ambiguous	0.3573	ambiguous	-1.355	Destabilizing	0.716	D	0.524	neutral	None	None	None	None	I
S/I	0.2289	likely_benign	0.2039	benign	-0.3	Destabilizing	0.264	N	0.52	neutral	None	None	None	None	I
S/K	0.8537	likely_pathogenic	0.8012	pathogenic	-0.548	Destabilizing	0.593	D	0.385	neutral	None	None	None	None	I
S/L	0.1358	likely_benign	0.1268	benign	-0.3	Destabilizing	0.129	N	0.505	neutral	None	None	None	None	I
S/M	0.1934	likely_benign	0.1832	benign	0.073	Stabilizing	0.836	D	0.522	neutral	None	None	None	None	I
S/N	0.2038	likely_benign	0.1717	benign	-0.327	Destabilizing	0.593	D	0.443	neutral	None	None	None	None	I
S/P	0.9318	likely_pathogenic	0.9196	pathogenic	-0.369	Destabilizing	0.921	D	0.513	neutral	D	0.530539314	None	None	I
S/Q	0.5798	likely_pathogenic	0.5101	ambiguous	-0.597	Destabilizing	0.94	D	0.468	neutral	None	None	None	None	I
S/R	0.7979	likely_pathogenic	0.7309	pathogenic	-0.409	Destabilizing	0.836	D	0.511	neutral	None	None	None	None	I
S/T	0.096	likely_benign	0.0937	benign	-0.433	Destabilizing	0.003	N	0.135	neutral	N	0.44243754	None	None	I
S/V	0.2159	likely_benign	0.2001	benign	-0.369	Destabilizing	0.129	N	0.503	neutral	None	None	None	None	I
S/W	0.4096	ambiguous	0.3732	ambiguous	-1.007	Destabilizing	0.951	D	0.54	neutral	None	None	None	None	I
S/Y	0.1767	likely_benign	0.1572	benign	-0.747	Destabilizing	0.001	N	0.219	neutral	N	0.505584941	None	None	I

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.