TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14984	45175;45176;45177	chr2:178621972;178621971;178621970	chr2:179486699;179486698;179486697
N2AB	13343	40252;40253;40254	chr2:178621972;178621971;178621970	chr2:179486699;179486698;179486697
N2A	12416	37471;37472;37473	chr2:178621972;178621971;178621970	chr2:179486699;179486698;179486697
N2B	5919	17980;17981;17982	chr2:178621972;178621971;178621970	chr2:179486699;179486698;179486697
Novex-1	6044	18355;18356;18357	chr2:178621972;178621971;178621970	chr2:179486699;179486698;179486697
Novex-2	6111	18556;18557;18558	chr2:178621972;178621971;178621970	chr2:179486699;179486698;179486697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-101
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.2513
• 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
G/C	rs555721876	-0.37	1.0	N	0.694	0.402	0.366848117066	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
G/C	rs555721876	-0.37	1.0	N	0.694	0.402	0.366848117066	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	6.58E-05	0	0	0	None	0	0	0	0	0
G/C	rs555721876	-0.37	1.0	N	0.694	0.402	0.366848117066	gnomAD-4.0.0	1.24192E-06	None	None	None	None	N	None	0	1.67774E-05	None	0	0	None	0	0	0	1.10076E-05	0
G/D	rs1190798574	None	1.0	N	0.639	0.421	0.252162846088	gnomAD-4.0.0	1.59892E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87028E-06	0	0
G/R	rs555721876	-0.213	1.0	D	0.68	0.426	0.325533332567	gnomAD-2.1.1	3.67E-05	None	None	None	None	N	None	0	0	None	0	5.13699E-04	None	0	None	0	0	0
G/R	rs555721876	-0.213	1.0	D	0.68	0.426	0.325533332567	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	1.95313E-04	None	0	0	0	0	0
G/R	rs555721876	-0.213	1.0	D	0.68	0.426	0.325533332567	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
G/R	rs555721876	-0.213	1.0	D	0.68	0.426	0.325533332567	gnomAD-4.0.0	9.93463E-06	None	None	None	None	N	None	0	0	None	0	2.92319E-04	None	0	0	8.48768E-07	0	3.20914E-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
G/A	0.4256	ambiguous	0.4666	ambiguous	-0.323	Destabilizing	1.0	D	0.553	neutral	N	0.460138509	None	None	N
G/C	0.7034	likely_pathogenic	0.7443	pathogenic	-0.758	Destabilizing	1.0	D	0.694	prob.neutral	N	0.508243773	None	None	N
G/D	0.6204	likely_pathogenic	0.6697	pathogenic	-0.744	Destabilizing	1.0	D	0.639	neutral	N	0.450385388	None	None	N
G/E	0.7366	likely_pathogenic	0.7633	pathogenic	-0.885	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
G/F	0.9477	likely_pathogenic	0.9556	pathogenic	-0.966	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
G/H	0.8812	likely_pathogenic	0.8925	pathogenic	-0.691	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
G/I	0.8867	likely_pathogenic	0.9023	pathogenic	-0.349	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
G/K	0.9197	likely_pathogenic	0.9328	pathogenic	-0.977	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
G/L	0.8849	likely_pathogenic	0.9077	pathogenic	-0.349	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
G/M	0.8923	likely_pathogenic	0.9053	pathogenic	-0.422	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
G/N	0.5708	likely_pathogenic	0.6191	pathogenic	-0.544	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
G/P	0.9882	likely_pathogenic	0.9901	pathogenic	-0.305	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
G/Q	0.8304	likely_pathogenic	0.8489	pathogenic	-0.808	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
G/R	0.8801	likely_pathogenic	0.8934	pathogenic	-0.536	Destabilizing	1.0	D	0.68	prob.neutral	D	0.538754232	None	None	N
G/S	0.2064	likely_benign	0.2209	benign	-0.669	Destabilizing	1.0	D	0.629	neutral	N	0.434116094	None	None	N
G/T	0.4617	ambiguous	0.4926	ambiguous	-0.743	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
G/V	0.7662	likely_pathogenic	0.794	pathogenic	-0.305	Destabilizing	1.0	D	0.694	prob.neutral	N	0.515825706	None	None	N
G/W	0.8702	likely_pathogenic	0.8826	pathogenic	-1.186	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
G/Y	0.902	likely_pathogenic	0.9163	pathogenic	-0.819	Destabilizing	1.0	D	0.678	prob.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.