TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4707	14344;14345;14346	chr2:178738334;178738333;178738332	chr2:179603061;179603060;179603059
N2AB	4390	13393;13394;13395	chr2:178738334;178738333;178738332	chr2:179603061;179603060;179603059
N2A	3463	10612;10613;10614	chr2:178738334;178738333;178738332	chr2:179603061;179603060;179603059
N2B	4344	13255;13256;13257	chr2:178738334;178738333;178738332	chr2:179603061;179603060;179603059
Novex-1	4469	13630;13631;13632	chr2:178738334;178738333;178738332	chr2:179603061;179603060;179603059
Novex-2	4536	13831;13832;13833	chr2:178738334;178738333;178738332	chr2:179603061;179603060;179603059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-30
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.843
• Predicted PPI site: I

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
E/K	rs749584249	0.597	0.935	N	0.347	0.174	0.275641507738	gnomAD-2.1.1	2.15E-05	None	None	None	None	I	None	0	0	None	9.71E-05	0	None	0	None	0	3.92E-05	0
E/K	rs749584249	0.597	0.935	N	0.347	0.174	0.275641507738	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	0	1.31096E-04	0	0	0	None	0	0	4.41E-05	0	0
E/K	rs749584249	0.597	0.935	N	0.347	0.174	0.275641507738	gnomAD-4.0.0	1.67438E-05	None	None	None	None	I	None	0	5.00684E-05	None	3.38089E-05	0	None	0	1.64636E-04	1.69619E-05	0	3.20523E-05
E/Q	rs749584249	0.281	0.336	N	0.225	0.108	0.235038932564	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.56E-05	None	0	0	0
E/Q	rs749584249	0.281	0.336	N	0.225	0.108	0.235038932564	gnomAD-4.0.0	1.36945E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.32148E-05	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
E/A	0.1517	likely_benign	0.1843	benign	-0.295	Destabilizing	0.064	N	0.163	neutral	N	0.482296626	None	None	I
E/C	0.8724	likely_pathogenic	0.9104	pathogenic	-0.44	Destabilizing	0.998	D	0.387	neutral	None	None	None	None	I
E/D	0.2092	likely_benign	0.2453	benign	-0.449	Destabilizing	0.016	N	0.173	neutral	N	0.502657247	None	None	I
E/F	0.7136	likely_pathogenic	0.7688	pathogenic	0.115	Stabilizing	0.98	D	0.456	neutral	None	None	None	None	I
E/G	0.1873	likely_benign	0.2316	benign	-0.528	Destabilizing	0.837	D	0.443	neutral	N	0.507447294	None	None	I
E/H	0.4919	ambiguous	0.5461	ambiguous	0.547	Stabilizing	0.98	D	0.384	neutral	None	None	None	None	I
E/I	0.3127	likely_benign	0.3729	ambiguous	0.301	Stabilizing	0.083	N	0.387	neutral	None	None	None	None	I
E/K	0.143	likely_benign	0.1891	benign	0.102	Stabilizing	0.935	D	0.347	neutral	N	0.489707053	None	None	I
E/L	0.321	likely_benign	0.39	ambiguous	0.301	Stabilizing	0.584	D	0.425	neutral	None	None	None	None	I
E/M	0.4059	ambiguous	0.4621	ambiguous	0.103	Stabilizing	0.98	D	0.425	neutral	None	None	None	None	I
E/N	0.3317	likely_benign	0.3717	ambiguous	-0.403	Destabilizing	0.872	D	0.384	neutral	None	None	None	None	I
E/P	0.6928	likely_pathogenic	0.7202	pathogenic	0.123	Stabilizing	0.932	D	0.441	neutral	None	None	None	None	I
E/Q	0.1211	likely_benign	0.1341	benign	-0.312	Destabilizing	0.336	N	0.225	neutral	N	0.448236627	None	None	I
E/R	0.2563	likely_benign	0.2924	benign	0.524	Stabilizing	0.872	D	0.367	neutral	None	None	None	None	I
E/S	0.2062	likely_benign	0.2364	benign	-0.57	Destabilizing	0.584	D	0.321	neutral	None	None	None	None	I
E/T	0.2181	likely_benign	0.2606	benign	-0.366	Destabilizing	0.083	N	0.186	neutral	None	None	None	None	I
E/V	0.1848	likely_benign	0.2279	benign	0.123	Stabilizing	0.514	D	0.395	neutral	N	0.500750526	None	None	I
E/W	0.9159	likely_pathogenic	0.9396	pathogenic	0.312	Stabilizing	0.998	D	0.402	neutral	None	None	None	None	I
E/Y	0.6383	likely_pathogenic	0.7047	pathogenic	0.366	Stabilizing	0.993	D	0.459	neutral	None	None	None	None	I

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.