TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2316	7171;7172;7173	chr2:178774318;178774317;178774316	chr2:179639045;179639044;179639043
N2AB	2316	7171;7172;7173	chr2:178774318;178774317;178774316	chr2:179639045;179639044;179639043
N2A	2316	7171;7172;7173	chr2:178774318;178774317;178774316	chr2:179639045;179639044;179639043
N2B	2270	7033;7034;7035	chr2:178774318;178774317;178774316	chr2:179639045;179639044;179639043
Novex-1	2270	7033;7034;7035	chr2:178774318;178774317;178774316	chr2:179639045;179639044;179639043
Novex-2	2270	7033;7034;7035	chr2:178774318;178774317;178774316	chr2:179639045;179639044;179639043
Novex-3	2316	7171;7172;7173	chr2:178774318;178774317;178774316	chr2:179639045;179639044;179639043

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-12
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.5629
• 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
S/C	None	None	1.0	N	0.733	0.491	0.659138129972	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
S/A	0.0786	likely_benign	0.0801	benign	-0.343	Destabilizing	0.997	D	0.595	neutral	N	0.495324496	None	None	N
S/C	0.1521	likely_benign	0.1628	benign	-0.206	Destabilizing	1.0	D	0.733	prob.delet.	N	0.51291992	None	None	N
S/D	0.5266	ambiguous	0.5601	ambiguous	-0.138	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
S/E	0.6165	likely_pathogenic	0.6373	pathogenic	-0.236	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
S/F	0.2342	likely_benign	0.2412	benign	-0.944	Destabilizing	1.0	D	0.788	deleterious	N	0.507091466	None	None	N
S/G	0.1164	likely_benign	0.1175	benign	-0.454	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/H	0.4222	ambiguous	0.4426	ambiguous	-1.026	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
S/I	0.2395	likely_benign	0.2416	benign	-0.182	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
S/K	0.7228	likely_pathogenic	0.7511	pathogenic	-0.521	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
S/L	0.1284	likely_benign	0.1303	benign	-0.182	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
S/M	0.2447	likely_benign	0.2473	benign	0.187	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
S/N	0.1638	likely_benign	0.1734	benign	-0.237	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
S/P	0.549	ambiguous	0.5787	pathogenic	-0.207	Destabilizing	1.0	D	0.758	deleterious	N	0.513623843	None	None	N
S/Q	0.5532	ambiguous	0.565	pathogenic	-0.542	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
S/R	0.6482	likely_pathogenic	0.6768	pathogenic	-0.276	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/T	0.0833	likely_benign	0.0847	benign	-0.319	Destabilizing	0.999	D	0.673	neutral	N	0.506715774	None	None	N
S/V	0.2046	likely_benign	0.2043	benign	-0.207	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
S/W	0.4391	ambiguous	0.458	ambiguous	-0.949	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
S/Y	0.2249	likely_benign	0.2323	benign	-0.673	Destabilizing	1.0	D	0.787	deleterious	D	0.548574619	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.