TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5226	15901;15902;15903	chr2:178733713;178733712;178733711	chr2:179598440;179598439;179598438
N2AB	4909	14950;14951;14952	chr2:178733713;178733712;178733711	chr2:179598440;179598439;179598438
N2A	3982	12169;12170;12171	chr2:178733713;178733712;178733711	chr2:179598440;179598439;179598438
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-35
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.1621
• 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
I/L	None	None	None	N	0.191	0.107	0.519296960841	gnomAD-4.0.0	4.77345E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29824E-05	0
I/M	None	None	0.108	N	0.445	0.059	0.370051654043	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
I/A	0.1243	likely_benign	0.1358	benign	-2.085	Highly Destabilizing	None	N	0.236	neutral	None	None	None	None	N
I/C	0.3605	ambiguous	0.3854	ambiguous	-1.354	Destabilizing	0.245	N	0.433	neutral	None	None	None	None	N
I/D	0.2914	likely_benign	0.31	benign	-2.0	Highly Destabilizing	0.018	N	0.468	neutral	None	None	None	None	N
I/E	0.194	likely_benign	0.2019	benign	-1.901	Destabilizing	0.009	N	0.415	neutral	None	None	None	None	N
I/F	0.0959	likely_benign	0.1029	benign	-1.259	Destabilizing	0.022	N	0.415	neutral	None	None	None	None	N
I/G	0.3276	likely_benign	0.3698	ambiguous	-2.51	Highly Destabilizing	0.009	N	0.405	neutral	None	None	None	None	N
I/H	0.1674	likely_benign	0.1595	benign	-1.845	Destabilizing	0.138	N	0.493	neutral	None	None	None	None	N
I/K	0.1371	likely_benign	0.1449	benign	-1.721	Destabilizing	0.007	N	0.424	neutral	N	0.474986431	None	None	N
I/L	0.0735	likely_benign	0.0761	benign	-0.93	Destabilizing	None	N	0.191	neutral	N	0.483810588	None	None	N
I/M	0.0634	likely_benign	0.0689	benign	-0.763	Destabilizing	0.108	N	0.445	neutral	N	0.512367928	None	None	N
I/N	0.0915	likely_benign	0.0934	benign	-1.714	Destabilizing	0.044	N	0.503	neutral	None	None	None	None	N
I/P	0.8021	likely_pathogenic	0.8688	pathogenic	-1.289	Destabilizing	0.085	N	0.524	neutral	None	None	None	None	N
I/Q	0.1383	likely_benign	0.1328	benign	-1.767	Destabilizing	0.001	N	0.467	neutral	None	None	None	None	N
I/R	0.1025	likely_benign	0.1072	benign	-1.196	Destabilizing	0.017	N	0.521	neutral	N	0.473962351	None	None	N
I/S	0.1004	likely_benign	0.1049	benign	-2.344	Highly Destabilizing	None	N	0.347	neutral	None	None	None	None	N
I/T	0.0687	likely_benign	0.071	benign	-2.127	Highly Destabilizing	None	N	0.239	neutral	N	0.398125079	None	None	N
I/V	0.0639	likely_benign	0.0684	benign	-1.289	Destabilizing	None	N	0.185	neutral	N	0.453520075	None	None	N
I/W	0.4705	ambiguous	0.5249	ambiguous	-1.514	Destabilizing	0.55	D	0.493	neutral	None	None	None	None	N
I/Y	0.2291	likely_benign	0.2353	benign	-1.266	Destabilizing	None	N	0.26	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.