TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27343	82252;82253;82254	chr2:178564105;178564104;178564103	chr2:179428832;179428831;179428830
N2AB	25702	77329;77330;77331	chr2:178564105;178564104;178564103	chr2:179428832;179428831;179428830
N2A	24775	74548;74549;74550	chr2:178564105;178564104;178564103	chr2:179428832;179428831;179428830
N2B	18278	55057;55058;55059	chr2:178564105;178564104;178564103	chr2:179428832;179428831;179428830
Novex-1	18403	55432;55433;55434	chr2:178564105;178564104;178564103	chr2:179428832;179428831;179428830
Novex-2	18470	55633;55634;55635	chr2:178564105;178564104;178564103	chr2:179428832;179428831;179428830
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: Ig-140
• Domain position: 66
• Structural Position: 149
• Q(SASA): 0.1214
• 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/G	None	None	1.0	D	0.817	0.838	0.712127334774	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
D/A	0.9301	likely_pathogenic	0.9573	pathogenic	0.516	Stabilizing	1.0	D	0.863	deleterious	D	0.63040694	None	None	N
D/C	0.9683	likely_pathogenic	0.979	pathogenic	0.433	Stabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
D/E	0.8349	likely_pathogenic	0.8845	pathogenic	-0.605	Destabilizing	1.0	D	0.576	neutral	D	0.617355717	None	None	N
D/F	0.9885	likely_pathogenic	0.994	pathogenic	1.197	Stabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
D/G	0.9507	likely_pathogenic	0.9692	pathogenic	0.039	Stabilizing	1.0	D	0.817	deleterious	D	0.656146856	None	None	N
D/H	0.8677	likely_pathogenic	0.9012	pathogenic	0.839	Stabilizing	1.0	D	0.875	deleterious	D	0.589253076	None	None	N
D/I	0.9842	likely_pathogenic	0.992	pathogenic	1.8	Stabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
D/K	0.9831	likely_pathogenic	0.9896	pathogenic	0.278	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
D/L	0.9829	likely_pathogenic	0.9905	pathogenic	1.8	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
D/M	0.9896	likely_pathogenic	0.9943	pathogenic	2.179	Highly Stabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
D/N	0.6434	likely_pathogenic	0.742	pathogenic	-0.565	Destabilizing	1.0	D	0.809	deleterious	D	0.612773145	None	None	N
D/P	0.9981	likely_pathogenic	0.9988	pathogenic	1.403	Stabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
D/Q	0.959	likely_pathogenic	0.9739	pathogenic	-0.211	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/R	0.9825	likely_pathogenic	0.9895	pathogenic	0.286	Stabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
D/S	0.8134	likely_pathogenic	0.8807	pathogenic	-0.843	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
D/T	0.9602	likely_pathogenic	0.9772	pathogenic	-0.405	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
D/V	0.9555	likely_pathogenic	0.975	pathogenic	1.403	Stabilizing	1.0	D	0.883	deleterious	D	0.656550465	None	None	N
D/W	0.9968	likely_pathogenic	0.9981	pathogenic	1.208	Stabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
D/Y	0.913	likely_pathogenic	0.9437	pathogenic	1.468	Stabilizing	1.0	D	0.903	deleterious	D	0.65634866	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.