TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25025	75298;75299;75300	chr2:178571059;178571058;178571057	chr2:179435786;179435785;179435784
N2AB	23384	70375;70376;70377	chr2:178571059;178571058;178571057	chr2:179435786;179435785;179435784
N2A	22457	67594;67595;67596	chr2:178571059;178571058;178571057	chr2:179435786;179435785;179435784
N2B	15960	48103;48104;48105	chr2:178571059;178571058;178571057	chr2:179435786;179435785;179435784
Novex-1	16085	48478;48479;48480	chr2:178571059;178571058;178571057	chr2:179435786;179435785;179435784
Novex-2	16152	48679;48680;48681	chr2:178571059;178571058;178571057	chr2:179435786;179435785;179435784
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-70
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1516
• 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
L/P	rs3731743	None	1.0	D	0.925	0.698	0.769630570616	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.94099E-04	None	0	0	0	0	0
L/P	rs3731743	None	1.0	D	0.925	0.698	0.769630570616	gnomAD-4.0.0	6.8216E-06	None	None	None	None	N	None	0	0	None	0	2.23145E-04	None	0	0	8.48274E-07	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
L/A	0.9609	likely_pathogenic	0.9564	pathogenic	-2.857	Highly Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
L/C	0.9319	likely_pathogenic	0.922	pathogenic	-1.871	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.588	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
L/E	0.9977	likely_pathogenic	0.9975	pathogenic	-3.255	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/F	0.7822	likely_pathogenic	0.7619	pathogenic	-1.711	Destabilizing	1.0	D	0.765	deleterious	N	0.519760202	None	None	N
L/G	0.9956	likely_pathogenic	0.9948	pathogenic	-3.465	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/H	0.9959	likely_pathogenic	0.9951	pathogenic	-3.169	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.550741699	None	None	N
L/I	0.1163	likely_benign	0.1161	benign	-1.011	Destabilizing	0.999	D	0.559	neutral	N	0.494044504	None	None	N
L/K	0.9965	likely_pathogenic	0.9962	pathogenic	-2.257	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/M	0.3842	ambiguous	0.3535	ambiguous	-1.137	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
L/N	0.9982	likely_pathogenic	0.9978	pathogenic	-3.032	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
L/P	0.9978	likely_pathogenic	0.9975	pathogenic	-1.62	Destabilizing	1.0	D	0.925	deleterious	D	0.55048821	None	None	N
L/Q	0.9926	likely_pathogenic	0.9908	pathogenic	-2.641	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/R	0.9928	likely_pathogenic	0.9919	pathogenic	-2.349	Highly Destabilizing	1.0	D	0.909	deleterious	D	0.55048821	None	None	N
L/S	0.9948	likely_pathogenic	0.9938	pathogenic	-3.524	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/T	0.9657	likely_pathogenic	0.9613	pathogenic	-3.027	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/V	0.1467	likely_benign	0.1472	benign	-1.62	Destabilizing	0.999	D	0.579	neutral	N	0.4646267	None	None	N
L/W	0.9892	likely_pathogenic	0.9867	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/Y	0.9875	likely_pathogenic	0.9862	pathogenic	-1.92	Destabilizing	1.0	D	0.836	deleterious	None	None	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.