TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22346	67261;67262;67263	chr2:178580343;178580342;178580341	chr2:179445070;179445069;179445068
N2AB	20705	62338;62339;62340	chr2:178580343;178580342;178580341	chr2:179445070;179445069;179445068
N2A	19778	59557;59558;59559	chr2:178580343;178580342;178580341	chr2:179445070;179445069;179445068
N2B	13281	40066;40067;40068	chr2:178580343;178580342;178580341	chr2:179445070;179445069;179445068
Novex-1	13406	40441;40442;40443	chr2:178580343;178580342;178580341	chr2:179445070;179445069;179445068
Novex-2	13473	40642;40643;40644	chr2:178580343;178580342;178580341	chr2:179445070;179445069;179445068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-126
• Domain position: 82
• Structural Position: 171
• Q(SASA): 0.5945
• 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
T/I	None	None	0.946	N	0.785	0.506	0.477219869099	gnomAD-4.0.0	6.84524E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99764E-07	0	0
T/N	rs1283475494	-0.08	0.973	N	0.753	0.435	0.432936702747	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	1.29249E-04	0	None	0	0	None	0	None	0	0	0
T/N	rs1283475494	-0.08	0.973	N	0.753	0.435	0.432936702747	gnomAD-4.0.0	2.05357E-06	None	None	None	None	I	None	8.97344E-05	0	None	0	0	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
T/A	0.142	likely_benign	0.1502	benign	-0.396	Destabilizing	0.016	N	0.351	neutral	N	0.490087329	None	None	I
T/C	0.606	likely_pathogenic	0.5763	pathogenic	-0.372	Destabilizing	0.994	D	0.757	deleterious	None	None	None	None	I
T/D	0.7697	likely_pathogenic	0.8046	pathogenic	0.345	Stabilizing	0.959	D	0.778	deleterious	None	None	None	None	I
T/E	0.668	likely_pathogenic	0.7041	pathogenic	0.321	Stabilizing	0.959	D	0.747	deleterious	None	None	None	None	I
T/F	0.4443	ambiguous	0.443	ambiguous	-0.631	Destabilizing	0.979	D	0.837	deleterious	None	None	None	None	I
T/G	0.4434	ambiguous	0.4729	ambiguous	-0.6	Destabilizing	0.769	D	0.725	prob.delet.	None	None	None	None	I
T/H	0.4744	ambiguous	0.4695	ambiguous	-0.8	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	I
T/I	0.3511	ambiguous	0.3361	benign	0.037	Stabilizing	0.946	D	0.785	deleterious	N	0.499343721	None	None	I
T/K	0.6043	likely_pathogenic	0.658	pathogenic	-0.415	Destabilizing	0.959	D	0.742	deleterious	None	None	None	None	I
T/L	0.2255	likely_benign	0.2299	benign	0.037	Stabilizing	0.769	D	0.645	neutral	None	None	None	None	I
T/M	0.1694	likely_benign	0.1539	benign	-0.017	Destabilizing	0.994	D	0.766	deleterious	None	None	None	None	I
T/N	0.2071	likely_benign	0.2294	benign	-0.311	Destabilizing	0.973	D	0.753	deleterious	N	0.518879526	None	None	I
T/P	0.279	likely_benign	0.3458	ambiguous	-0.075	Destabilizing	0.946	D	0.791	deleterious	N	0.4998507	None	None	I
T/Q	0.4728	ambiguous	0.4962	ambiguous	-0.424	Destabilizing	0.979	D	0.787	deleterious	None	None	None	None	I
T/R	0.53	ambiguous	0.5824	pathogenic	-0.213	Destabilizing	0.959	D	0.784	deleterious	None	None	None	None	I
T/S	0.1664	likely_benign	0.1751	benign	-0.57	Destabilizing	0.716	D	0.501	neutral	N	0.516164507	None	None	I
T/V	0.2276	likely_benign	0.2209	benign	-0.075	Destabilizing	0.769	D	0.558	neutral	None	None	None	None	I
T/W	0.8319	likely_pathogenic	0.8147	pathogenic	-0.646	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	I
T/Y	0.48	ambiguous	0.4677	ambiguous	-0.363	Destabilizing	0.993	D	0.835	deleterious	None	None	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.