TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28360	85303;85304;85305	chr2:178561054;178561053;178561052	chr2:179425781;179425780;179425779
N2AB	26719	80380;80381;80382	chr2:178561054;178561053;178561052	chr2:179425781;179425780;179425779
N2A	25792	77599;77600;77601	chr2:178561054;178561053;178561052	chr2:179425781;179425780;179425779
N2B	19295	58108;58109;58110	chr2:178561054;178561053;178561052	chr2:179425781;179425780;179425779
Novex-1	19420	58483;58484;58485	chr2:178561054;178561053;178561052	chr2:179425781;179425780;179425779
Novex-2	19487	58684;58685;58686	chr2:178561054;178561053;178561052	chr2:179425781;179425780;179425779
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-143
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.7834
• Predicted PPI site: I

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/H	None	None	0.901	D	0.457	0.624	0.489104616352	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.579	likely_pathogenic	0.547	ambiguous	-0.317	Destabilizing	0.722	D	0.43	neutral	D	0.534963709	None	None	I
D/C	0.9552	likely_pathogenic	0.951	pathogenic	-0.29	Destabilizing	0.996	D	0.645	neutral	None	None	None	None	I
D/E	0.566	likely_pathogenic	0.5533	ambiguous	-0.406	Destabilizing	0.014	N	0.098	neutral	D	0.525808285	None	None	I
D/F	0.9658	likely_pathogenic	0.9624	pathogenic	0.055	Stabilizing	0.987	D	0.587	neutral	None	None	None	None	I
D/G	0.5254	ambiguous	0.506	ambiguous	-0.573	Destabilizing	0.565	D	0.413	neutral	D	0.535470688	None	None	I
D/H	0.7807	likely_pathogenic	0.7723	pathogenic	0.28	Stabilizing	0.901	D	0.457	neutral	D	0.535977667	None	None	I
D/I	0.9299	likely_pathogenic	0.9253	pathogenic	0.327	Stabilizing	0.961	D	0.579	neutral	None	None	None	None	I
D/K	0.9147	likely_pathogenic	0.9061	pathogenic	-0.003	Destabilizing	0.633	D	0.409	neutral	None	None	None	None	I
D/L	0.8783	likely_pathogenic	0.8677	pathogenic	0.327	Stabilizing	0.961	D	0.566	neutral	None	None	None	None	I
D/M	0.9561	likely_pathogenic	0.9499	pathogenic	0.315	Stabilizing	0.996	D	0.59	neutral	None	None	None	None	I
D/N	0.3468	ambiguous	0.3398	benign	-0.463	Destabilizing	0.008	N	0.205	neutral	D	0.53445673	None	None	I
D/P	0.8425	likely_pathogenic	0.8403	pathogenic	0.135	Stabilizing	0.961	D	0.451	neutral	None	None	None	None	I
D/Q	0.8716	likely_pathogenic	0.8624	pathogenic	-0.37	Destabilizing	0.923	D	0.369	neutral	None	None	None	None	I
D/R	0.907	likely_pathogenic	0.898	pathogenic	0.35	Stabilizing	0.923	D	0.503	neutral	None	None	None	None	I
D/S	0.4584	ambiguous	0.4428	ambiguous	-0.59	Destabilizing	0.633	D	0.353	neutral	None	None	None	None	I
D/T	0.7747	likely_pathogenic	0.7605	pathogenic	-0.382	Destabilizing	0.775	D	0.421	neutral	None	None	None	None	I
D/V	0.7646	likely_pathogenic	0.7507	pathogenic	0.135	Stabilizing	0.949	D	0.559	neutral	D	0.535977667	None	None	I
D/W	0.9847	likely_pathogenic	0.9831	pathogenic	0.246	Stabilizing	0.996	D	0.671	neutral	None	None	None	None	I
D/Y	0.7436	likely_pathogenic	0.7196	pathogenic	0.301	Stabilizing	0.983	D	0.589	neutral	D	0.536231156	None	None	I

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.