TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30433	91522;91523;91524	chr2:178551234;178551233;178551232	chr2:179415961;179415960;179415959
N2AB	28792	86599;86600;86601	chr2:178551234;178551233;178551232	chr2:179415961;179415960;179415959
N2A	27865	83818;83819;83820	chr2:178551234;178551233;178551232	chr2:179415961;179415960;179415959
N2B	21368	64327;64328;64329	chr2:178551234;178551233;178551232	chr2:179415961;179415960;179415959
Novex-1	21493	64702;64703;64704	chr2:178551234;178551233;178551232	chr2:179415961;179415960;179415959
Novex-2	21560	64903;64904;64905	chr2:178551234;178551233;178551232	chr2:179415961;179415960;179415959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-110
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4907
• 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
D/E	None	None	1.0	N	0.387	0.271	0.185906805712	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85971E-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
D/A	0.6108	likely_pathogenic	0.6802	pathogenic	-0.513	Destabilizing	1.0	D	0.683	prob.neutral	N	0.496527449	None	None	N
D/C	0.9469	likely_pathogenic	0.9589	pathogenic	-0.156	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
D/E	0.6048	likely_pathogenic	0.6513	pathogenic	-0.409	Destabilizing	1.0	D	0.387	neutral	N	0.45535283	None	None	N
D/F	0.9325	likely_pathogenic	0.9463	pathogenic	-0.101	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
D/G	0.7171	likely_pathogenic	0.7923	pathogenic	-0.789	Destabilizing	1.0	D	0.705	prob.neutral	N	0.469407002	None	None	N
D/H	0.7991	likely_pathogenic	0.8395	pathogenic	-0.027	Destabilizing	1.0	D	0.601	neutral	N	0.478512036	None	None	N
D/I	0.8693	likely_pathogenic	0.894	pathogenic	0.194	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
D/K	0.9316	likely_pathogenic	0.9507	pathogenic	0.175	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
D/L	0.8388	likely_pathogenic	0.8642	pathogenic	0.194	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
D/M	0.9342	likely_pathogenic	0.9482	pathogenic	0.389	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
D/N	0.3487	ambiguous	0.4117	ambiguous	-0.411	Destabilizing	1.0	D	0.635	neutral	N	0.482443431	None	None	N
D/P	0.9962	likely_pathogenic	0.9975	pathogenic	-0.019	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
D/Q	0.871	likely_pathogenic	0.8966	pathogenic	-0.317	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
D/R	0.9088	likely_pathogenic	0.9319	pathogenic	0.416	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
D/S	0.4294	ambiguous	0.502	ambiguous	-0.53	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
D/T	0.7485	likely_pathogenic	0.7973	pathogenic	-0.296	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/V	0.7302	likely_pathogenic	0.771	pathogenic	-0.019	Destabilizing	1.0	D	0.703	prob.neutral	N	0.476092499	None	None	N
D/W	0.9858	likely_pathogenic	0.9891	pathogenic	0.162	Stabilizing	1.0	D	0.62	neutral	None	None	None	None	N
D/Y	0.7352	likely_pathogenic	0.7787	pathogenic	0.175	Stabilizing	1.0	D	0.606	neutral	N	0.504845497	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.