TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32538	97837;97838;97839	chr2:178541465;178541464;178541463	chr2:179406192;179406191;179406190
N2AB	30897	92914;92915;92916	chr2:178541465;178541464;178541463	chr2:179406192;179406191;179406190
N2A	29970	90133;90134;90135	chr2:178541465;178541464;178541463	chr2:179406192;179406191;179406190
N2B	23473	70642;70643;70644	chr2:178541465;178541464;178541463	chr2:179406192;179406191;179406190
Novex-1	23598	71017;71018;71019	chr2:178541465;178541464;178541463	chr2:179406192;179406191;179406190
Novex-2	23665	71218;71219;71220	chr2:178541465;178541464;178541463	chr2:179406192;179406191;179406190
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-125
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1923
• 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
R/C	rs761050391	-1.608	1.0	N	0.873	0.47	0.434716162284	gnomAD-2.1.1	1.24785E-04	None	None	None	None	N	None	0	5.81E-05	None	0	5.59E-05	None	8.51064E-04	None	0	1.78E-05	0
R/C	rs761050391	-1.608	1.0	N	0.873	0.47	0.434716162284	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	8.28157E-04	0
R/C	rs761050391	-1.608	1.0	N	0.873	0.47	0.434716162284	gnomAD-4.0.0	5.45485E-05	None	None	None	None	N	None	0	6.67089E-05	None	0	2.23015E-05	None	0	4.93421E-04	6.78214E-06	7.46826E-04	6.40677E-05
R/H	rs3731749	-1.877	1.0	N	0.836	0.482	None	gnomAD-2.1.1	1.71898E-01	None	None	None	None	N	None	7.14108E-02	1.45161E-01	None	1.68765E-01	4.29855E-01	None	2.53193E-01	None	1.51237E-01	1.44664E-01	1.60231E-01
R/H	rs3731749	-1.877	1.0	N	0.836	0.482	None	gnomAD-3.1.2	1.41555E-01	None	None	None	None	N	None	7.53709E-02	1.28015E-01	4.72588E-01	1.70317E-01	4.40411E-01	None	1.62656E-01	1.13924E-01	1.45474E-01	2.56841E-01	1.25958E-01
R/H	rs3731749	-1.877	1.0	N	0.836	0.482	None	1000 genomes	2.09265E-01	None	None	None	None	N	None	6.66E-02	1.484E-01	None	None	4.514E-01	1.382E-01	None	None	None	2.689E-01	None
R/H	rs3731749	-1.877	1.0	N	0.836	0.482	None	gnomAD-4.0.0	1.52606E-01	None	None	None	None	N	None	7.34376E-02	1.40731E-01	None	1.68007E-01	4.34368E-01	None	1.53036E-01	1.25372E-01	1.38994E-01	2.50687E-01	1.61359E-01
R/L	rs3731749	None	1.0	N	0.831	0.468	0.367042808489	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/L	rs3731749	None	1.0	N	0.831	0.468	0.367042808489	gnomAD-4.0.0	6.58033E-06	None	None	None	None	N	None	2.41616E-05	0	None	0	0	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
R/A	0.9266	likely_pathogenic	0.9372	pathogenic	-1.756	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
R/C	0.3724	ambiguous	0.3975	ambiguous	-1.64	Destabilizing	1.0	D	0.873	deleterious	N	0.482481146	None	None	N
R/D	0.9894	likely_pathogenic	0.9904	pathogenic	-0.678	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
R/E	0.86	likely_pathogenic	0.8631	pathogenic	-0.451	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
R/F	0.9203	likely_pathogenic	0.9293	pathogenic	-0.945	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
R/G	0.875	likely_pathogenic	0.8788	pathogenic	-2.143	Highly Destabilizing	1.0	D	0.831	deleterious	N	0.478521581	None	None	N
R/H	0.3348	likely_benign	0.3343	benign	-1.867	Destabilizing	1.0	D	0.836	deleterious	N	0.472178479	None	None	N
R/I	0.7949	likely_pathogenic	0.8232	pathogenic	-0.641	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
R/K	0.2001	likely_benign	0.2144	benign	-1.109	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
R/L	0.7717	likely_pathogenic	0.7956	pathogenic	-0.641	Destabilizing	1.0	D	0.831	deleterious	N	0.516265216	None	None	N
R/M	0.6911	likely_pathogenic	0.7332	pathogenic	-1.119	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
R/N	0.9663	likely_pathogenic	0.9701	pathogenic	-1.133	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
R/P	0.9984	likely_pathogenic	0.9987	pathogenic	-0.999	Destabilizing	1.0	D	0.871	deleterious	N	0.496879326	None	None	N
R/Q	0.2065	likely_benign	0.2057	benign	-1.032	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
R/S	0.9437	likely_pathogenic	0.9482	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.814	deleterious	N	0.467645802	None	None	N
R/T	0.8534	likely_pathogenic	0.8723	pathogenic	-1.627	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
R/V	0.8374	likely_pathogenic	0.8559	pathogenic	-0.999	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
R/W	0.483	ambiguous	0.501	ambiguous	-0.404	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
R/Y	0.7582	likely_pathogenic	0.7728	pathogenic	-0.26	Destabilizing	1.0	D	0.885	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.