TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24535	73828;73829;73830	chr2:178572529;178572528;178572527	chr2:179437256;179437255;179437254
N2AB	22894	68905;68906;68907	chr2:178572529;178572528;178572527	chr2:179437256;179437255;179437254
N2A	21967	66124;66125;66126	chr2:178572529;178572528;178572527	chr2:179437256;179437255;179437254
N2B	15470	46633;46634;46635	chr2:178572529;178572528;178572527	chr2:179437256;179437255;179437254
Novex-1	15595	47008;47009;47010	chr2:178572529;178572528;178572527	chr2:179437256;179437255;179437254
Novex-2	15662	47209;47210;47211	chr2:178572529;178572528;178572527	chr2:179437256;179437255;179437254
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-66
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.089
• 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	0.756	0.474	0.678686674281	gnomAD-4.0.0	6.84357E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65695E-05
S/F	rs201804005	None	1.0	N	0.8	0.468	0.829790380963	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/F	rs201804005	None	1.0	N	0.8	0.468	0.829790380963	gnomAD-4.0.0	6.57428E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47046E-05	0	0
S/P	None	None	0.997	D	0.761	0.532	0.488477830397	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79918E-06	0	0
S/Y	rs201804005	-0.966	1.0	N	0.797	0.482	None	gnomAD-2.1.1	4.43256E-04	None	None	None	None	N	None	0	8.49E-05	None	7.54936E-03	0	None	1.63463E-04	None	3.19949E-04	2.19099E-04	2.81215E-04
S/Y	rs201804005	-0.966	1.0	N	0.797	0.482	None	gnomAD-3.1.2	3.81308E-04	None	None	None	None	N	None	2.41E-05	0	0	1.06567E-02	0	None	3.76506E-04	0	2.20569E-04	0	4.78011E-04
S/Y	rs201804005	-0.966	1.0	N	0.797	0.482	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
S/Y	rs201804005	-0.966	1.0	N	0.797	0.482	None	gnomAD-4.0.0	3.2291E-04	None	None	None	None	N	None	1.33305E-05	5.001E-05	None	8.41557E-03	0	None	4.53083E-04	1.65235E-04	1.56831E-04	1.20799E-04	6.72366E-04

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	0.0873	likely_benign	0.0802	benign	-0.612	Destabilizing	0.64	D	0.431	neutral	N	0.497370895	None	None	N
S/C	0.108	likely_benign	0.1145	benign	-0.889	Destabilizing	1.0	D	0.756	deleterious	N	0.498246722	None	None	N
S/D	0.7757	likely_pathogenic	0.7124	pathogenic	-1.607	Destabilizing	0.984	D	0.507	neutral	None	None	None	None	N
S/E	0.7918	likely_pathogenic	0.7504	pathogenic	-1.55	Destabilizing	0.988	D	0.505	neutral	None	None	None	None	N
S/F	0.2359	likely_benign	0.2186	benign	-0.836	Destabilizing	1.0	D	0.8	deleterious	N	0.510172458	None	None	N
S/G	0.1427	likely_benign	0.1383	benign	-0.871	Destabilizing	0.991	D	0.435	neutral	None	None	None	None	N
S/H	0.4797	ambiguous	0.4496	ambiguous	-1.363	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/I	0.3893	ambiguous	0.3662	ambiguous	-0.02	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
S/K	0.9186	likely_pathogenic	0.8913	pathogenic	-0.7	Destabilizing	1.0	D	0.503	neutral	None	None	None	None	N
S/L	0.183	likely_benign	0.168	benign	-0.02	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
S/M	0.2018	likely_benign	0.2006	benign	0.118	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
S/N	0.3168	likely_benign	0.2899	benign	-1.076	Destabilizing	0.875	D	0.513	neutral	None	None	None	None	N
S/P	0.9956	likely_pathogenic	0.9926	pathogenic	-0.184	Destabilizing	0.997	D	0.761	deleterious	D	0.557737274	None	None	N
S/Q	0.6904	likely_pathogenic	0.6558	pathogenic	-1.231	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
S/R	0.8911	likely_pathogenic	0.8582	pathogenic	-0.618	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
S/T	0.1056	likely_benign	0.0974	benign	-0.845	Destabilizing	0.003	N	0.357	neutral	N	0.515561501	None	None	N
S/V	0.3145	likely_benign	0.2953	benign	-0.184	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
S/W	0.5197	ambiguous	0.4715	ambiguous	-0.955	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
S/Y	0.2749	likely_benign	0.2476	benign	-0.568	Destabilizing	1.0	D	0.797	deleterious	N	0.490560493	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.