TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25580	76963;76964;76965	chr2:178569394;178569393;178569392	chr2:179434121;179434120;179434119
N2AB	23939	72040;72041;72042	chr2:178569394;178569393;178569392	chr2:179434121;179434120;179434119
N2A	23012	69259;69260;69261	chr2:178569394;178569393;178569392	chr2:179434121;179434120;179434119
N2B	16515	49768;49769;49770	chr2:178569394;178569393;178569392	chr2:179434121;179434120;179434119
Novex-1	16640	50143;50144;50145	chr2:178569394;178569393;178569392	chr2:179434121;179434120;179434119
Novex-2	16707	50344;50345;50346	chr2:178569394;178569393;178569392	chr2:179434121;179434120;179434119
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-135
• Domain position: 67
• Structural Position: 155
• Q(SASA): 0.319
• 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
T/A	rs371711135	-1.426	0.892	N	0.478	0.248	None	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	8.27E-05	0	None	0	2.05719E-04	None	0	None	0	0	0
T/A	rs371711135	-1.426	0.892	N	0.478	0.248	None	gnomAD-3.1.2	9.86E-05	None	None	None	None	N	None	1.93097E-04	6.56E-05	0	0	7.73395E-04	None	0	0	0	0	9.56023E-04
T/A	rs371711135	-1.426	0.892	N	0.478	0.248	None	gnomAD-4.0.0	1.6736E-05	None	None	None	None	N	None	2.00342E-04	1.66822E-05	None	0	1.33875E-04	None	0	0	0	0	8.00769E-05
T/K	rs56372592	-0.29	0.993	N	0.644	0.324	None	gnomAD-2.1.1	2.11159E-04	None	None	None	None	N	None	1.24131E-04	8.5E-05	None	0	0	None	0	None	4E-05	3.84259E-04	4.21941E-04
T/K	rs56372592	-0.29	0.993	N	0.644	0.324	None	gnomAD-3.1.2	2.36774E-04	None	None	None	None	N	None	9.66E-05	6.57E-05	0	0	0	None	0	0	4.26496E-04	0	9.56938E-04
T/K	rs56372592	-0.29	0.993	N	0.644	0.324	None	gnomAD-4.0.0	6.51499E-04	None	None	None	None	N	None	8.01518E-05	1.5018E-04	None	3.38021E-05	0	None	3.1252E-05	0	8.49471E-04	0	4.96524E-04
T/M	rs56372592	-0.241	0.998	N	0.664	0.36	None	gnomAD-2.1.1	1.61769E-03	None	None	None	None	N	None	6.62032E-04	1.41659E-04	None	0	2.0426E-02	None	2.28953E-04	None	0	1.56841E-04	9.84529E-04
T/M	rs56372592	-0.241	0.998	N	0.664	0.36	None	gnomAD-3.1.2	9.3394E-04	None	None	None	None	N	None	5.31144E-04	4.59559E-04	0	0	1.95433E-02	None	0	0	8.82E-05	2.06782E-04	2.39234E-03
T/M	rs56372592	-0.241	0.998	N	0.664	0.36	None	1000 genomes	4.59265E-03	None	None	None	None	N	None	0	0	None	None	2.28E-02	0	None	None	None	0	None
T/M	rs56372592	-0.241	0.998	N	0.664	0.36	None	gnomAD-4.0.0	5.79551E-04	None	None	None	None	N	None	5.06802E-04	3.16941E-04	None	0	1.28566E-02	None	0	0	8.47781E-05	2.85589E-04	2.81807E-03
T/R	None	None	0.998	N	0.649	0.335	0.370789594751	gnomAD-4.0.0	6.84389E-07	None	None	None	None	N	None	0	0	None	0	2.52232E-05	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
T/A	0.1103	likely_benign	0.1158	benign	-1.184	Destabilizing	0.892	D	0.478	neutral	N	0.47448484	None	None	N
T/C	0.3234	likely_benign	0.3526	ambiguous	-0.72	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
T/D	0.575	likely_pathogenic	0.6068	pathogenic	-0.839	Destabilizing	0.996	D	0.646	neutral	None	None	None	None	N
T/E	0.4218	ambiguous	0.4415	ambiguous	-0.634	Destabilizing	0.996	D	0.637	neutral	None	None	None	None	N
T/F	0.1906	likely_benign	0.2028	benign	-0.916	Destabilizing	0.975	D	0.687	prob.neutral	None	None	None	None	N
T/G	0.3872	ambiguous	0.4083	ambiguous	-1.602	Destabilizing	0.987	D	0.609	neutral	None	None	None	None	N
T/H	0.2229	likely_benign	0.245	benign	-1.643	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
T/I	0.1012	likely_benign	0.0947	benign	-0.084	Destabilizing	0.033	N	0.367	neutral	None	None	None	None	N
T/K	0.3097	likely_benign	0.3283	benign	-0.199	Destabilizing	0.993	D	0.644	neutral	N	0.493633499	None	None	N
T/L	0.0836	likely_benign	0.0862	benign	-0.084	Destabilizing	0.437	N	0.513	neutral	None	None	None	None	N
T/M	0.0772	likely_benign	0.0785	benign	-0.126	Destabilizing	0.998	D	0.664	neutral	N	0.458039653	None	None	N
T/N	0.1354	likely_benign	0.1391	benign	-0.842	Destabilizing	0.996	D	0.567	neutral	None	None	None	None	N
T/P	0.6695	likely_pathogenic	0.6809	pathogenic	-0.42	Destabilizing	0.994	D	0.642	neutral	N	0.490894028	None	None	N
T/Q	0.2612	likely_benign	0.2748	benign	-0.618	Destabilizing	0.996	D	0.662	neutral	None	None	None	None	N
T/R	0.2408	likely_benign	0.2642	benign	-0.48	Destabilizing	0.998	D	0.649	neutral	N	0.472103433	None	None	N
T/S	0.116	likely_benign	0.1217	benign	-1.193	Destabilizing	0.944	D	0.422	neutral	N	0.489073041	None	None	N
T/V	0.0962	likely_benign	0.0947	benign	-0.42	Destabilizing	0.437	N	0.473	neutral	None	None	None	None	N
T/W	0.6353	likely_pathogenic	0.6729	pathogenic	-0.961	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
T/Y	0.2461	likely_benign	0.2693	benign	-0.591	Destabilizing	0.987	D	0.708	prob.delet.	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.