TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2527	7804;7805;7806	chr2:178773477;178773476;178773475	chr2:179638204;179638203;179638202
N2AB	2527	7804;7805;7806	chr2:178773477;178773476;178773475	chr2:179638204;179638203;179638202
N2A	2527	7804;7805;7806	chr2:178773477;178773476;178773475	chr2:179638204;179638203;179638202
N2B	2481	7666;7667;7668	chr2:178773477;178773476;178773475	chr2:179638204;179638203;179638202
Novex-1	2481	7666;7667;7668	chr2:178773477;178773476;178773475	chr2:179638204;179638203;179638202
Novex-2	2481	7666;7667;7668	chr2:178773477;178773476;178773475	chr2:179638204;179638203;179638202
Novex-3	2527	7804;7805;7806	chr2:178773477;178773476;178773475	chr2:179638204;179638203;179638202

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-14
• Domain position: 83
• Structural Position: 173
• Q(SASA): 0.466
• 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
N/D	rs773079394	-0.801	None	N	0.193	0.107	0.104622674875	gnomAD-2.1.1	7.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	7.77E-06	0
N/D	rs773079394	-0.801	None	N	0.193	0.107	0.104622674875	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs773079394	-0.801	None	N	0.193	0.107	0.104622674875	gnomAD-4.0.0	2.56138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39191E-06	1.34002E-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
N/A	0.183	likely_benign	0.1781	benign	-0.662	Destabilizing	0.035	N	0.439	neutral	None	None	None	None	N
N/C	0.1886	likely_benign	0.1901	benign	0.204	Stabilizing	0.935	D	0.574	neutral	None	None	None	None	N
N/D	0.1227	likely_benign	0.1157	benign	-0.476	Destabilizing	None	N	0.193	neutral	N	0.443471533	None	None	N
N/E	0.2611	likely_benign	0.2439	benign	-0.46	Destabilizing	0.035	N	0.541	neutral	None	None	None	None	N
N/F	0.2987	likely_benign	0.2934	benign	-0.774	Destabilizing	0.791	D	0.597	neutral	None	None	None	None	N
N/G	0.2731	likely_benign	0.2612	benign	-0.917	Destabilizing	0.067	N	0.516	neutral	None	None	None	None	N
N/H	0.0651	likely_benign	0.0663	benign	-0.895	Destabilizing	0.484	N	0.589	neutral	N	0.45258781	None	None	N
N/I	0.1233	likely_benign	0.1226	benign	-0.054	Destabilizing	0.317	N	0.601	neutral	N	0.49395313	None	None	N
N/K	0.1511	likely_benign	0.1428	benign	-0.139	Destabilizing	0.027	N	0.529	neutral	N	0.437056892	None	None	N
N/L	0.1458	likely_benign	0.1475	benign	-0.054	Destabilizing	0.149	N	0.539	neutral	None	None	None	None	N
N/M	0.237	likely_benign	0.2315	benign	0.544	Stabilizing	0.935	D	0.575	neutral	None	None	None	None	N
N/P	0.65	likely_pathogenic	0.6231	pathogenic	-0.228	Destabilizing	0.555	D	0.607	neutral	None	None	None	None	N
N/Q	0.1963	likely_benign	0.1909	benign	-0.783	Destabilizing	0.149	N	0.586	neutral	None	None	None	None	N
N/R	0.1569	likely_benign	0.1483	benign	-0.056	Destabilizing	0.001	N	0.269	neutral	None	None	None	None	N
N/S	0.0784	likely_benign	0.0795	benign	-0.548	Destabilizing	0.005	N	0.19	neutral	N	0.447742343	None	None	N
N/T	0.1033	likely_benign	0.0983	benign	-0.368	Destabilizing	0.002	N	0.185	neutral	N	0.434599291	None	None	N
N/V	0.1477	likely_benign	0.1458	benign	-0.228	Destabilizing	0.149	N	0.577	neutral	None	None	None	None	N
N/W	0.5964	likely_pathogenic	0.585	pathogenic	-0.609	Destabilizing	0.935	D	0.606	neutral	None	None	None	None	N
N/Y	0.1011	likely_benign	0.1016	benign	-0.388	Destabilizing	0.741	D	0.599	neutral	N	0.452405878	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.