TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16141	48646;48647;48648	chr2:178615680;178615679;178615678	chr2:179480407;179480406;179480405
N2AB	14500	43723;43724;43725	chr2:178615680;178615679;178615678	chr2:179480407;179480406;179480405
N2A	13573	40942;40943;40944	chr2:178615680;178615679;178615678	chr2:179480407;179480406;179480405
N2B	7076	21451;21452;21453	chr2:178615680;178615679;178615678	chr2:179480407;179480406;179480405
Novex-1	7201	21826;21827;21828	chr2:178615680;178615679;178615678	chr2:179480407;179480406;179480405
Novex-2	7268	22027;22028;22029	chr2:178615680;178615679;178615678	chr2:179480407;179480406;179480405
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-4
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.1132
• 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
A/V	None	None	0.998	N	0.68	0.339	0.475192790171	gnomAD-4.0.0	2.7388E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60022E-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
A/C	0.4457	ambiguous	0.43	ambiguous	-0.993	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
A/D	0.729	likely_pathogenic	0.7104	pathogenic	-1.932	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
A/E	0.6747	likely_pathogenic	0.6706	pathogenic	-1.857	Destabilizing	0.999	D	0.711	prob.delet.	D	0.638596672	None	None	N
A/F	0.5888	likely_pathogenic	0.5984	pathogenic	-0.913	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
A/G	0.2248	likely_benign	0.2293	benign	-1.481	Destabilizing	0.996	D	0.654	neutral	N	0.519650353	None	None	N
A/H	0.7819	likely_pathogenic	0.7836	pathogenic	-1.842	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/I	0.3743	ambiguous	0.3691	ambiguous	-0.207	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/K	0.8007	likely_pathogenic	0.8083	pathogenic	-1.467	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
A/L	0.3724	ambiguous	0.3684	ambiguous	-0.207	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
A/M	0.4111	ambiguous	0.4164	ambiguous	-0.21	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/N	0.633	likely_pathogenic	0.6245	pathogenic	-1.369	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
A/P	0.9475	likely_pathogenic	0.942	pathogenic	-0.467	Destabilizing	1.0	D	0.745	deleterious	D	0.602989408	None	None	N
A/Q	0.6643	likely_pathogenic	0.6554	pathogenic	-1.382	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
A/R	0.6884	likely_pathogenic	0.6941	pathogenic	-1.271	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
A/S	0.1266	likely_benign	0.1262	benign	-1.729	Destabilizing	0.957	D	0.432	neutral	N	0.452270806	None	None	N
A/T	0.1217	likely_benign	0.1291	benign	-1.555	Destabilizing	0.996	D	0.676	prob.neutral	N	0.515899743	None	None	N
A/V	0.1743	likely_benign	0.1745	benign	-0.467	Destabilizing	0.998	D	0.68	prob.neutral	N	0.494273535	None	None	N
A/W	0.9279	likely_pathogenic	0.9237	pathogenic	-1.5	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
A/Y	0.7487	likely_pathogenic	0.7444	pathogenic	-1.023	Destabilizing	1.0	D	0.837	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.