TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20740	62443;62444;62445	chr2:178589507;178589506;178589505	chr2:179454234;179454233;179454232
N2AB	19099	57520;57521;57522	chr2:178589507;178589506;178589505	chr2:179454234;179454233;179454232
N2A	18172	54739;54740;54741	chr2:178589507;178589506;178589505	chr2:179454234;179454233;179454232
N2B	11675	35248;35249;35250	chr2:178589507;178589506;178589505	chr2:179454234;179454233;179454232
Novex-1	11800	35623;35624;35625	chr2:178589507;178589506;178589505	chr2:179454234;179454233;179454232
Novex-2	11867	35824;35825;35826	chr2:178589507;178589506;178589505	chr2:179454234;179454233;179454232
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-38
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2057
• 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
E/D	rs766362512	-1.568	0.183	N	0.501	0.093	0.290222751274	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/D	rs766362512	-1.568	0.183	N	0.501	0.093	0.290222751274	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	2.28812E-05	None	0	0	None	0	0	0	0	0
E/K	rs1451572769	-0.358	0.101	N	0.525	0.183	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/K	rs1451572769	-0.358	0.101	N	0.525	0.183	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1451572769	-0.358	0.101	N	0.525	0.183	None	gnomAD-4.0.0	1.36367E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69542E-05	0	3.20318E-05
E/V	rs559490402	0.916	0.351	N	0.617	0.222	0.312001716656	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/V	rs559490402	0.916	0.351	N	0.617	0.222	0.312001716656	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
E/V	rs559490402	0.916	0.351	N	0.617	0.222	0.312001716656	gnomAD-4.0.0	4.33895E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93408E-06	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
E/A	0.266	likely_benign	0.3898	ambiguous	-1.035	Destabilizing	0.047	N	0.482	neutral	N	0.497530313	None	None	N
E/C	0.8056	likely_pathogenic	0.8792	pathogenic	-0.387	Destabilizing	0.983	D	0.617	neutral	None	None	None	None	N
E/D	0.4701	ambiguous	0.5729	pathogenic	-1.457	Destabilizing	0.183	N	0.501	neutral	N	0.474170396	None	None	N
E/F	0.7534	likely_pathogenic	0.8681	pathogenic	-0.574	Destabilizing	0.94	D	0.581	neutral	None	None	None	None	N
E/G	0.5323	ambiguous	0.6244	pathogenic	-1.48	Destabilizing	0.001	N	0.486	neutral	N	0.492363556	None	None	N
E/H	0.5794	likely_pathogenic	0.7088	pathogenic	-0.632	Destabilizing	0.716	D	0.575	neutral	None	None	None	None	N
E/I	0.3629	ambiguous	0.5433	ambiguous	0.238	Stabilizing	0.716	D	0.616	neutral	None	None	None	None	N
E/K	0.4032	ambiguous	0.56	ambiguous	-1.027	Destabilizing	0.101	N	0.525	neutral	N	0.478077761	None	None	N
E/L	0.4371	ambiguous	0.6225	pathogenic	0.238	Stabilizing	0.418	N	0.613	neutral	None	None	None	None	N
E/M	0.461	ambiguous	0.6325	pathogenic	0.927	Stabilizing	0.836	D	0.56	neutral	None	None	None	None	N
E/N	0.5516	ambiguous	0.6984	pathogenic	-1.385	Destabilizing	0.418	N	0.567	neutral	None	None	None	None	N
E/P	0.9943	likely_pathogenic	0.9965	pathogenic	-0.17	Destabilizing	0.593	D	0.602	neutral	None	None	None	None	N
E/Q	0.1456	likely_benign	0.1939	benign	-1.037	Destabilizing	0.001	N	0.21	neutral	N	0.419800249	None	None	N
E/R	0.4994	ambiguous	0.6314	pathogenic	-0.963	Destabilizing	0.264	N	0.569	neutral	None	None	None	None	N
E/S	0.3194	likely_benign	0.4338	ambiguous	-2.035	Highly Destabilizing	0.129	N	0.491	neutral	None	None	None	None	N
E/T	0.2995	likely_benign	0.4227	ambiguous	-1.612	Destabilizing	0.004	N	0.351	neutral	None	None	None	None	N
E/V	0.2497	likely_benign	0.3968	ambiguous	-0.17	Destabilizing	0.351	N	0.617	neutral	N	0.49683688	None	None	N
E/W	0.9265	likely_pathogenic	0.9606	pathogenic	-0.648	Destabilizing	0.983	D	0.629	neutral	None	None	None	None	N
E/Y	0.7004	likely_pathogenic	0.8213	pathogenic	-0.361	Destabilizing	0.836	D	0.569	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.