TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3388	10387;10388;10389	chr2:178759125;178759124;178759123	chr2:179623852;179623851;179623850
N2AB	3388	10387;10388;10389	chr2:178759125;178759124;178759123	chr2:179623852;179623851;179623850
N2A	3388	10387;10388;10389	chr2:178759125;178759124;178759123	chr2:179623852;179623851;179623850
N2B	3342	10249;10250;10251	chr2:178759125;178759124;178759123	chr2:179623852;179623851;179623850
Novex-1	3342	10249;10250;10251	chr2:178759125;178759124;178759123	chr2:179623852;179623851;179623850
Novex-2	3342	10249;10250;10251	chr2:178759125;178759124;178759123	chr2:179623852;179623851;179623850
Novex-3	3388	10387;10388;10389	chr2:178759125;178759124;178759123	chr2:179623852;179623851;179623850

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Ig-24
• Domain position: 44
• Structural Position: 111
• Q(SASA): 0.672
• 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/L	None	None	0.82	N	0.284	0.343	0.604606306746	gnomAD-4.0.0	6.84125E-07	None	None	None	None	N	None	2.98704E-05	0	None	0	0	None	0	0	0	0	0
R/Q	rs187703540	0.182	0.91	N	0.233	0.179	None	gnomAD-2.1.1	7.165E-04	None	None	None	None	N	None	2.80404E-04	5.65E-05	None	0	9.19506E-03	None	2.6137E-04	None	0	7.79E-06	1.38927E-04
R/Q	rs187703540	0.182	0.91	N	0.233	0.179	None	gnomAD-3.1.2	5.12901E-04	None	None	None	None	N	None	2.65675E-04	0	0	0	1.1946E-02	None	0	0	1.47E-05	6.21118E-04	4.78469E-04
R/Q	rs187703540	0.182	0.91	N	0.233	0.179	None	1000 genomes	3.79393E-03	None	None	None	None	N	None	0	0	None	None	1.88E-02	0	None	None	None	0	None
R/Q	rs187703540	0.182	0.91	N	0.233	0.179	None	gnomAD-4.0.0	2.17483E-04	None	None	None	None	N	None	2.5332E-04	3.33344E-05	None	0	6.19954E-03	None	0	0	5.08503E-06	2.19597E-04	4.15987E-04
R/W	rs758680640	-0.461	0.999	D	0.22	0.483	0.431379191433	gnomAD-2.1.1	2.13E-05	None	None	None	None	N	None	0	8.47E-05	None	0	5.02E-05	None	3.27E-05	None	0	7.79E-06	0
R/W	rs758680640	-0.461	0.999	D	0.22	0.483	0.431379191433	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.55E-05	0	0	1.92678E-04	None	0	0	0	0	0
R/W	rs758680640	-0.461	0.999	D	0.22	0.483	0.431379191433	gnomAD-4.0.0	4.0897E-05	None	None	None	None	N	None	1.33504E-05	8.33556E-05	None	0	2.22965E-05	None	0	0	4.83078E-05	1.09818E-05	1.60061E-05

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	0.418	ambiguous	0.557	ambiguous	0.029	Stabilizing	0.495	N	0.291	neutral	None	None	None	None	N
R/C	0.2711	likely_benign	0.3273	benign	-0.386	Destabilizing	0.995	D	0.193	neutral	None	None	None	None	N
R/D	0.6367	likely_pathogenic	0.7488	pathogenic	-0.329	Destabilizing	0.003	N	0.141	neutral	None	None	None	None	N
R/E	0.4445	ambiguous	0.5706	pathogenic	-0.282	Destabilizing	0.013	N	0.121	neutral	None	None	None	None	N
R/F	0.733	likely_pathogenic	0.8231	pathogenic	-0.36	Destabilizing	0.981	D	0.209	neutral	None	None	None	None	N
R/G	0.3036	likely_benign	0.3997	ambiguous	-0.098	Destabilizing	0.653	D	0.237	neutral	N	0.492105614	None	None	N
R/H	0.1344	likely_benign	0.165	benign	-0.697	Destabilizing	0.981	D	0.227	neutral	None	None	None	None	N
R/I	0.3699	ambiguous	0.5025	ambiguous	0.316	Stabilizing	0.944	D	0.249	neutral	None	None	None	None	N
R/K	0.1816	likely_benign	0.2202	benign	-0.224	Destabilizing	0.003	N	0.127	neutral	None	None	None	None	N
R/L	0.2952	likely_benign	0.4037	ambiguous	0.316	Stabilizing	0.82	D	0.284	neutral	N	0.492871788	None	None	N
R/M	0.4735	ambiguous	0.5856	pathogenic	-0.193	Destabilizing	0.981	D	0.229	neutral	None	None	None	None	N
R/N	0.5872	likely_pathogenic	0.6999	pathogenic	-0.27	Destabilizing	0.704	D	0.213	neutral	None	None	None	None	N
R/P	0.3375	likely_benign	0.4505	ambiguous	0.238	Stabilizing	0.902	D	0.283	neutral	N	0.479148754	None	None	N
R/Q	0.1344	likely_benign	0.1684	benign	-0.24	Destabilizing	0.91	D	0.233	neutral	N	0.50237116	None	None	N
R/S	0.4605	ambiguous	0.598	pathogenic	-0.394	Destabilizing	0.495	N	0.27	neutral	None	None	None	None	N
R/T	0.3237	likely_benign	0.453	ambiguous	-0.24	Destabilizing	0.704	D	0.271	neutral	None	None	None	None	N
R/V	0.4663	ambiguous	0.5817	pathogenic	0.238	Stabilizing	0.828	D	0.308	neutral	None	None	None	None	N
R/W	0.3077	likely_benign	0.3258	benign	-0.606	Destabilizing	0.999	D	0.22	neutral	D	0.580528872	None	None	N
R/Y	0.487	ambiguous	0.5966	pathogenic	-0.182	Destabilizing	0.981	D	0.229	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.