TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21571	64936;64937;64938	chr2:178584930;178584929;178584928	chr2:179449657;179449656;179449655
N2AB	19930	60013;60014;60015	chr2:178584930;178584929;178584928	chr2:179449657;179449656;179449655
N2A	19003	57232;57233;57234	chr2:178584930;178584929;178584928	chr2:179449657;179449656;179449655
N2B	12506	37741;37742;37743	chr2:178584930;178584929;178584928	chr2:179449657;179449656;179449655
Novex-1	12631	38116;38117;38118	chr2:178584930;178584929;178584928	chr2:179449657;179449656;179449655
Novex-2	12698	38317;38318;38319	chr2:178584930;178584929;178584928	chr2:179449657;179449656;179449655
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: Fn3-44
• Domain position: 13
• Structural Position: 14
• Q(SASA): 0.7611
• 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/N	rs750771623	0.596	0.22	N	0.505	0.198	0.198526703765	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
D/N	rs750771623	0.596	0.22	N	0.505	0.198	0.198526703765	gnomAD-4.0.0	4.77737E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.5802E-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	0.1831	likely_benign	0.1983	benign	-0.275	Destabilizing	0.124	N	0.488	neutral	N	0.466088866	None	None	N
D/C	0.621	likely_pathogenic	0.6094	pathogenic	0.212	Stabilizing	0.968	D	0.647	neutral	None	None	None	None	N
D/E	0.1026	likely_benign	0.1094	benign	-0.213	Destabilizing	None	N	0.083	neutral	N	0.420605538	None	None	N
D/F	0.686	likely_pathogenic	0.6986	pathogenic	-0.365	Destabilizing	0.89	D	0.579	neutral	None	None	None	None	N
D/G	0.2031	likely_benign	0.2161	benign	-0.439	Destabilizing	0.001	N	0.161	neutral	N	0.476484119	None	None	N
D/H	0.346	ambiguous	0.3726	ambiguous	-0.236	Destabilizing	0.667	D	0.521	neutral	N	0.495628786	None	None	N
D/I	0.4734	ambiguous	0.5051	ambiguous	0.1	Stabilizing	0.726	D	0.573	neutral	None	None	None	None	N
D/K	0.4154	ambiguous	0.4501	ambiguous	0.48	Stabilizing	0.157	N	0.463	neutral	None	None	None	None	N
D/L	0.4591	ambiguous	0.4802	ambiguous	0.1	Stabilizing	0.567	D	0.522	neutral	None	None	None	None	N
D/M	0.61	likely_pathogenic	0.6248	pathogenic	0.332	Stabilizing	0.968	D	0.568	neutral	None	None	None	None	N
D/N	0.1171	likely_benign	0.1233	benign	0.239	Stabilizing	0.22	N	0.505	neutral	N	0.474362665	None	None	N
D/P	0.8759	likely_pathogenic	0.906	pathogenic	-0.004	Destabilizing	0.726	D	0.482	neutral	None	None	None	None	N
D/Q	0.3094	likely_benign	0.3348	benign	0.249	Stabilizing	0.396	N	0.454	neutral	None	None	None	None	N
D/R	0.4809	ambiguous	0.5182	ambiguous	0.527	Stabilizing	0.396	N	0.521	neutral	None	None	None	None	N
D/S	0.1417	likely_benign	0.1475	benign	0.139	Stabilizing	0.157	N	0.463	neutral	None	None	None	None	N
D/T	0.2677	likely_benign	0.2882	benign	0.269	Stabilizing	0.272	N	0.473	neutral	None	None	None	None	N
D/V	0.2878	likely_benign	0.3099	benign	-0.004	Destabilizing	0.497	N	0.502	neutral	N	0.469673718	None	None	N
D/W	0.9069	likely_pathogenic	0.9165	pathogenic	-0.271	Destabilizing	0.968	D	0.673	neutral	None	None	None	None	N
D/Y	0.351	ambiguous	0.357	ambiguous	-0.134	Destabilizing	0.859	D	0.579	neutral	N	0.502376735	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.