TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28977	87154;87155;87156	chr2:178558530;178558529;178558528	chr2:179423257;179423256;179423255
N2AB	27336	82231;82232;82233	chr2:178558530;178558529;178558528	chr2:179423257;179423256;179423255
N2A	26409	79450;79451;79452	chr2:178558530;178558529;178558528	chr2:179423257;179423256;179423255
N2B	19912	59959;59960;59961	chr2:178558530;178558529;178558528	chr2:179423257;179423256;179423255
Novex-1	20037	60334;60335;60336	chr2:178558530;178558529;178558528	chr2:179423257;179423256;179423255
Novex-2	20104	60535;60536;60537	chr2:178558530;178558529;178558528	chr2:179423257;179423256;179423255
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-99
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.117
• 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
Y/C	rs776958326	-1.697	1.0	D	0.856	0.852	0.871318523177	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
Y/C	rs776958326	-1.697	1.0	D	0.856	0.852	0.871318523177	gnomAD-4.0.0	2.05267E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69838E-06	0	0
Y/H	None	None	1.0	D	0.803	0.884	0.757445817929	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85812E-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
Y/A	0.9927	likely_pathogenic	0.9945	pathogenic	-3.469	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/C	0.8223	likely_pathogenic	0.8631	pathogenic	-1.744	Destabilizing	1.0	D	0.856	deleterious	D	0.656530823	None	None	N
Y/D	0.9945	likely_pathogenic	0.9952	pathogenic	-3.751	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.656732627	None	None	N
Y/E	0.9985	likely_pathogenic	0.9987	pathogenic	-3.542	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/F	0.2053	likely_benign	0.2249	benign	-1.355	Destabilizing	0.999	D	0.642	neutral	D	0.561395113	None	None	N
Y/G	0.9827	likely_pathogenic	0.9852	pathogenic	-3.854	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/H	0.9457	likely_pathogenic	0.9576	pathogenic	-2.505	Highly Destabilizing	1.0	D	0.803	deleterious	D	0.656127214	None	None	N
Y/I	0.9564	likely_pathogenic	0.9652	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/K	0.9978	likely_pathogenic	0.9982	pathogenic	-2.317	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/L	0.9228	likely_pathogenic	0.9412	pathogenic	-2.156	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
Y/M	0.9744	likely_pathogenic	0.982	pathogenic	-1.821	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.9667	likely_pathogenic	0.9726	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.656530823	None	None	N
Y/P	0.9991	likely_pathogenic	0.9992	pathogenic	-2.613	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
Y/Q	0.9956	likely_pathogenic	0.9967	pathogenic	-2.833	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/R	0.989	likely_pathogenic	0.9913	pathogenic	-2.073	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/S	0.9719	likely_pathogenic	0.9791	pathogenic	-3.361	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.656530823	None	None	N
Y/T	0.9883	likely_pathogenic	0.9914	pathogenic	-3.042	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/V	0.9227	likely_pathogenic	0.9386	pathogenic	-2.613	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
Y/W	0.8278	likely_pathogenic	0.8382	pathogenic	-0.567	Destabilizing	1.0	D	0.794	deleterious	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.