TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27214	81865;81866;81867	chr2:178564492;178564491;178564490	chr2:179429219;179429218;179429217
N2AB	25573	76942;76943;76944	chr2:178564492;178564491;178564490	chr2:179429219;179429218;179429217
N2A	24646	74161;74162;74163	chr2:178564492;178564491;178564490	chr2:179429219;179429218;179429217
N2B	18149	54670;54671;54672	chr2:178564492;178564491;178564490	chr2:179429219;179429218;179429217
Novex-1	18274	55045;55046;55047	chr2:178564492;178564491;178564490	chr2:179429219;179429218;179429217
Novex-2	18341	55246;55247;55248	chr2:178564492;178564491;178564490	chr2:179429219;179429218;179429217
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: Fn3-86
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4805
• 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/A	rs1704936651	None	0.865	N	0.537	0.347	0.410337123052	gnomAD-4.0.0	3.42485E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50043E-06	0	0
D/N	None	None	0.978	N	0.591	0.351	0.360961692134	gnomAD-4.0.0	6.85014E-07	None	None	None	None	N	None	0	0	None	0	2.5328E-05	None	0	0	0	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	0.1341	likely_benign	0.1191	benign	0.055	Stabilizing	0.865	D	0.537	neutral	N	0.46695669	None	None	N
D/C	0.5411	ambiguous	0.4875	ambiguous	-0.124	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
D/E	0.0965	likely_benign	0.0865	benign	-0.328	Destabilizing	0.039	N	0.314	neutral	N	0.434420197	None	None	N
D/F	0.5349	ambiguous	0.4772	ambiguous	-0.073	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
D/G	0.1353	likely_benign	0.1196	benign	-0.049	Destabilizing	0.928	D	0.548	neutral	N	0.448888218	None	None	N
D/H	0.2628	likely_benign	0.2214	benign	0.525	Stabilizing	0.997	D	0.696	prob.neutral	N	0.470661223	None	None	N
D/I	0.3382	likely_benign	0.2997	benign	0.258	Stabilizing	0.992	D	0.773	deleterious	None	None	None	None	N
D/K	0.3041	likely_benign	0.2536	benign	0.433	Stabilizing	0.968	D	0.609	neutral	None	None	None	None	N
D/L	0.3254	likely_benign	0.2861	benign	0.258	Stabilizing	0.983	D	0.744	deleterious	None	None	None	None	N
D/M	0.5089	ambiguous	0.4552	ambiguous	0.05	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
D/N	0.0866	likely_benign	0.0802	benign	0.233	Stabilizing	0.978	D	0.591	neutral	N	0.466783332	None	None	N
D/P	0.7018	likely_pathogenic	0.658	pathogenic	0.209	Stabilizing	0.992	D	0.643	neutral	None	None	None	None	N
D/Q	0.2484	likely_benign	0.2142	benign	0.223	Stabilizing	0.968	D	0.649	neutral	None	None	None	None	N
D/R	0.3849	ambiguous	0.3156	benign	0.647	Stabilizing	0.983	D	0.691	prob.neutral	None	None	None	None	N
D/S	0.1041	likely_benign	0.0924	benign	0.135	Stabilizing	0.895	D	0.475	neutral	None	None	None	None	N
D/T	0.1947	likely_benign	0.171	benign	0.22	Stabilizing	0.983	D	0.633	neutral	None	None	None	None	N
D/V	0.1984	likely_benign	0.1783	benign	0.209	Stabilizing	0.978	D	0.729	prob.delet.	N	0.470105018	None	None	N
D/W	0.8521	likely_pathogenic	0.8175	pathogenic	-0.05	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
D/Y	0.2363	likely_benign	0.2118	benign	0.149	Stabilizing	0.999	D	0.776	deleterious	N	0.488551668	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.