TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29700	89323;89324;89325	chr2:178554013;178554012;178554011	chr2:179418740;179418739;179418738
N2AB	28059	84400;84401;84402	chr2:178554013;178554012;178554011	chr2:179418740;179418739;179418738
N2A	27132	81619;81620;81621	chr2:178554013;178554012;178554011	chr2:179418740;179418739;179418738
N2B	20635	62128;62129;62130	chr2:178554013;178554012;178554011	chr2:179418740;179418739;179418738
Novex-1	20760	62503;62504;62505	chr2:178554013;178554012;178554011	chr2:179418740;179418739;179418738
Novex-2	20827	62704;62705;62706	chr2:178554013;178554012;178554011	chr2:179418740;179418739;179418738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-104
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4842
• 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/K	rs1301227457	0.21	0.999	N	0.691	0.365	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/K	rs1301227457	0.21	0.999	N	0.691	0.365	None	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02407E-05
E/V	rs763490789	-0.096	1.0	N	0.643	0.588	0.690242091961	gnomAD-4.0.0	2.053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47802E-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
E/A	0.2515	likely_benign	0.2216	benign	-0.359	Destabilizing	0.999	D	0.665	neutral	N	0.514246418	None	None	N
E/C	0.9318	likely_pathogenic	0.9172	pathogenic	0.223	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
E/D	0.3876	ambiguous	0.3111	benign	-0.5	Destabilizing	0.999	D	0.565	neutral	N	0.499641257	None	None	N
E/F	0.945	likely_pathogenic	0.9229	pathogenic	-0.551	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/G	0.3468	ambiguous	0.3034	benign	-0.558	Destabilizing	1.0	D	0.635	neutral	N	0.498248905	None	None	N
E/H	0.8324	likely_pathogenic	0.7633	pathogenic	-0.619	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
E/I	0.6127	likely_pathogenic	0.56	ambiguous	0.128	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
E/K	0.3148	likely_benign	0.2565	benign	0.321	Stabilizing	0.999	D	0.691	prob.neutral	N	0.481345965	None	None	N
E/L	0.7401	likely_pathogenic	0.6882	pathogenic	0.128	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
E/M	0.7385	likely_pathogenic	0.6806	pathogenic	0.456	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	N
E/N	0.5869	likely_pathogenic	0.5075	ambiguous	0.145	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/P	0.4954	ambiguous	0.4559	ambiguous	-0.013	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
E/Q	0.2592	likely_benign	0.2157	benign	0.143	Stabilizing	1.0	D	0.684	prob.neutral	N	0.485055721	None	None	N
E/R	0.5033	ambiguous	0.4186	ambiguous	0.333	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/S	0.4403	ambiguous	0.3767	ambiguous	-0.027	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
E/T	0.4805	ambiguous	0.4356	ambiguous	0.127	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
E/V	0.4111	ambiguous	0.3615	ambiguous	-0.013	Destabilizing	1.0	D	0.643	neutral	N	0.501616267	None	None	N
E/W	0.9819	likely_pathogenic	0.9695	pathogenic	-0.504	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/Y	0.9095	likely_pathogenic	0.8705	pathogenic	-0.325	Destabilizing	1.0	D	0.628	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.