TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14170	42733;42734;42735	chr2:178633991;178633990;178633989	chr2:179498718;179498717;179498716
N2AB	12529	37810;37811;37812	chr2:178633991;178633990;178633989	chr2:179498718;179498717;179498716
N2A	11602	35029;35030;35031	chr2:178633991;178633990;178633989	chr2:179498718;179498717;179498716
N2B	5105	15538;15539;15540	chr2:178633991;178633990;178633989	chr2:179498718;179498717;179498716
Novex-1	5230	15913;15914;15915	chr2:178633991;178633990;178633989	chr2:179498718;179498717;179498716
Novex-2	5297	16114;16115;16116	chr2:178633991;178633990;178633989	chr2:179498718;179498717;179498716
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-92
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.2988
• 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
M/I	rs1380128621	-1.73	0.01	N	0.106	0.226	0.477143196806	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
M/I	rs1380128621	-1.73	0.01	N	0.106	0.226	0.477143196806	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/I	rs1380128621	-1.73	0.01	N	0.106	0.226	0.477143196806	gnomAD-4.0.0	6.84371E-07	None	None	None	None	N	None	0	2.23654E-05	None	0	0	None	0	0	0	0	0
M/R	rs369623392	None	0.991	N	0.55	0.534	0.719157461425	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
M/R	rs369623392	None	0.991	N	0.55	0.534	0.719157461425	gnomAD-4.0.0	6.58233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07039E-04	0
M/T	rs369623392	-1.227	0.679	N	0.422	0.359	None	gnomAD-2.1.1	1.28754E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	1.99872E-04	2.35195E-04	1.40687E-04
M/T	rs369623392	-1.227	0.679	N	0.422	0.359	None	gnomAD-3.1.2	7.24E-05	None	None	None	None	N	None	4.83E-05	6.56E-05	0	0	0	None	0	0	1.17723E-04	0	0
M/T	rs369623392	-1.227	0.679	N	0.422	0.359	None	gnomAD-4.0.0	1.53118E-04	None	None	None	None	N	None	4.0093E-05	3.336E-05	None	0	0	None	1.56304E-04	0	1.91606E-04	0	9.61169E-05
M/V	None	None	0.01	N	0.105	0.203	0.44711355012	gnomAD-4.0.0	1.59213E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86013E-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
M/A	0.5992	likely_pathogenic	0.5951	pathogenic	-2.066	Highly Destabilizing	0.55	D	0.354	neutral	None	None	None	None	N
M/C	0.8505	likely_pathogenic	0.8621	pathogenic	-1.176	Destabilizing	0.993	D	0.498	neutral	None	None	None	None	N
M/D	0.8864	likely_pathogenic	0.8983	pathogenic	-0.974	Destabilizing	0.993	D	0.591	neutral	None	None	None	None	N
M/E	0.6308	likely_pathogenic	0.6273	pathogenic	-0.92	Destabilizing	0.977	D	0.511	neutral	None	None	None	None	N
M/F	0.4923	ambiguous	0.4909	ambiguous	-1.036	Destabilizing	0.932	D	0.421	neutral	None	None	None	None	N
M/G	0.7899	likely_pathogenic	0.8002	pathogenic	-2.364	Highly Destabilizing	0.977	D	0.547	neutral	None	None	None	None	N
M/H	0.7179	likely_pathogenic	0.7043	pathogenic	-1.31	Destabilizing	0.993	D	0.505	neutral	None	None	None	None	N
M/I	0.5513	ambiguous	0.5148	ambiguous	-1.269	Destabilizing	0.01	N	0.106	neutral	N	0.427663395	None	None	N
M/K	0.4428	ambiguous	0.3689	ambiguous	-0.941	Destabilizing	0.969	D	0.495	neutral	N	0.503216728	None	None	N
M/L	0.2327	likely_benign	0.2165	benign	-1.269	Destabilizing	0.166	N	0.17	neutral	N	0.481265152	None	None	N
M/N	0.6303	likely_pathogenic	0.6265	pathogenic	-0.803	Destabilizing	0.993	D	0.551	neutral	None	None	None	None	N
M/P	0.9011	likely_pathogenic	0.8843	pathogenic	-1.514	Destabilizing	0.993	D	0.56	neutral	None	None	None	None	N
M/Q	0.3459	ambiguous	0.3598	ambiguous	-0.864	Destabilizing	0.993	D	0.489	neutral	None	None	None	None	N
M/R	0.4991	ambiguous	0.4232	ambiguous	-0.41	Destabilizing	0.991	D	0.55	neutral	N	0.492245011	None	None	N
M/S	0.615	likely_pathogenic	0.6143	pathogenic	-1.347	Destabilizing	0.932	D	0.443	neutral	None	None	None	None	N
M/T	0.4546	ambiguous	0.4148	ambiguous	-1.19	Destabilizing	0.679	D	0.422	neutral	N	0.477807057	None	None	N
M/V	0.2038	likely_benign	0.1796	benign	-1.514	Destabilizing	0.01	N	0.105	neutral	N	0.362786381	None	None	N
M/W	0.7994	likely_pathogenic	0.7806	pathogenic	-0.934	Destabilizing	0.998	D	0.487	neutral	None	None	None	None	N
M/Y	0.6649	likely_pathogenic	0.6597	pathogenic	-1.022	Destabilizing	0.993	D	0.549	neutral	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.