TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5988	18187;18188;18189	chr2:178730571;178730570;178730569	chr2:179595298;179595297;179595296
N2AB	5671	17236;17237;17238	chr2:178730571;178730570;178730569	chr2:179595298;179595297;179595296
N2A	4744	14455;14456;14457	chr2:178730571;178730570;178730569	chr2:179595298;179595297;179595296
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-43
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3874
• 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
T/I	rs749765281	0.125	0.627	N	0.556	0.167	0.438278051908	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	8.69E-05	None	0	0	None	0	None	0	8.88E-06	1.65673E-04
T/I	rs749765281	0.125	0.627	N	0.556	0.167	0.438278051908	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30993E-04	0	0	0	None	0	0	0	0	0
T/I	rs749765281	0.125	0.627	N	0.556	0.167	0.438278051908	gnomAD-4.0.0	1.40954E-05	None	None	None	None	N	None	0	1.35607E-04	None	0	0	None	0	0	2.3938E-06	1.34037E-05	2.84527E-05

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	0.0731	likely_benign	0.0719	benign	-0.912	Destabilizing	0.09	N	0.434	neutral	D	0.526381501	None	None	N
T/C	0.3545	ambiguous	0.3433	ambiguous	-0.665	Destabilizing	0.944	D	0.545	neutral	None	None	None	None	N
T/D	0.2461	likely_benign	0.2636	benign	-1.214	Destabilizing	0.241	N	0.514	neutral	None	None	None	None	N
T/E	0.2562	likely_benign	0.2611	benign	-1.186	Destabilizing	0.241	N	0.508	neutral	None	None	None	None	N
T/F	0.1485	likely_benign	0.1482	benign	-1.097	Destabilizing	0.818	D	0.603	neutral	None	None	None	None	N
T/G	0.2431	likely_benign	0.2402	benign	-1.179	Destabilizing	0.116	N	0.531	neutral	None	None	None	None	N
T/H	0.1662	likely_benign	0.1657	benign	-1.555	Destabilizing	0.818	D	0.587	neutral	None	None	None	None	N
T/I	0.087	likely_benign	0.0828	benign	-0.281	Destabilizing	0.627	D	0.556	neutral	N	0.50285128	None	None	N
T/K	0.1494	likely_benign	0.1513	benign	-0.808	Destabilizing	0.193	N	0.503	neutral	N	0.489092549	None	None	N
T/L	0.0781	likely_benign	0.0726	benign	-0.281	Destabilizing	0.388	N	0.508	neutral	None	None	None	None	N
T/M	0.0845	likely_benign	0.079	benign	0.196	Stabilizing	0.981	D	0.551	neutral	None	None	None	None	N
T/N	0.0786	likely_benign	0.0828	benign	-1.002	Destabilizing	0.008	N	0.262	neutral	None	None	None	None	N
T/P	0.1658	likely_benign	0.1426	benign	-0.46	Destabilizing	0.773	D	0.555	neutral	N	0.499113004	None	None	N
T/Q	0.1761	likely_benign	0.1709	benign	-1.215	Destabilizing	0.69	D	0.565	neutral	None	None	None	None	N
T/R	0.1244	likely_benign	0.1241	benign	-0.562	Destabilizing	0.627	D	0.553	neutral	N	0.487767185	None	None	N
T/S	0.0875	likely_benign	0.0899	benign	-1.155	Destabilizing	0.001	N	0.197	neutral	N	0.492364928	None	None	N
T/V	0.0891	likely_benign	0.0867	benign	-0.46	Destabilizing	0.388	N	0.474	neutral	None	None	None	None	N
T/W	0.4308	ambiguous	0.4256	ambiguous	-1.093	Destabilizing	0.981	D	0.637	neutral	None	None	None	None	N
T/Y	0.1681	likely_benign	0.1746	benign	-0.796	Destabilizing	0.932	D	0.599	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.