TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33104	99535;99536;99537	chr2:178537897;178537896;178537895	chr2:179402624;179402623;179402622
N2AB	31463	94612;94613;94614	chr2:178537897;178537896;178537895	chr2:179402624;179402623;179402622
N2A	30536	91831;91832;91833	chr2:178537897;178537896;178537895	chr2:179402624;179402623;179402622
N2B	24039	72340;72341;72342	chr2:178537897;178537896;178537895	chr2:179402624;179402623;179402622
Novex-1	24164	72715;72716;72717	chr2:178537897;178537896;178537895	chr2:179402624;179402623;179402622
Novex-2	24231	72916;72917;72918	chr2:178537897;178537896;178537895	chr2:179402624;179402623;179402622
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: Ig-156
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5455
• 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	rs766169253	-0.398	1.0	N	0.701	0.371	None	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	6.54E-05	0	None	0	1.69396E-04	None	0	None	0	2.72E-05	0
R/C	rs766169253	-0.398	1.0	N	0.701	0.371	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	2.94E-05	0	4.79846E-04
R/C	rs766169253	-0.398	1.0	N	0.701	0.371	None	gnomAD-4.0.0	4.40852E-05	None	None	None	None	N	None	5.34817E-05	0	None	0	4.46369E-05	None	1.57129E-05	0	5.00874E-05	0	8.01899E-05
R/H	rs758617553	-0.918	0.995	N	0.533	0.248	0.15556083564	gnomAD-2.1.1	1.09E-05	None	None	None	None	N	None	4.16E-05	0	None	0	0	None	3.31E-05	None	0	7.95E-06	0
R/H	rs758617553	-0.918	0.995	N	0.533	0.248	0.15556083564	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/H	rs758617553	-0.918	0.995	N	0.533	0.248	0.15556083564	gnomAD-4.0.0	6.82943E-06	None	None	None	None	N	None	1.33711E-05	0	None	0	0	None	0	0	5.94218E-06	2.20347E-05	1.60375E-05
R/L	rs758617553	None	0.821	N	0.5	0.181	0.338592109245	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/L	rs758617553	None	0.821	N	0.5	0.181	0.338592109245	gnomAD-4.0.0	6.57471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47042E-05	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	0.7749	likely_pathogenic	0.7367	pathogenic	-0.185	Destabilizing	0.852	D	0.522	neutral	None	None	None	None	N
R/C	0.4832	ambiguous	0.4075	ambiguous	-0.351	Destabilizing	1.0	D	0.701	prob.neutral	N	0.461021259	None	None	N
R/D	0.929	likely_pathogenic	0.916	pathogenic	-0.032	Destabilizing	0.953	D	0.553	neutral	None	None	None	None	N
R/E	0.6974	likely_pathogenic	0.6326	pathogenic	0.072	Stabilizing	0.465	N	0.501	neutral	None	None	None	None	N
R/F	0.8311	likely_pathogenic	0.817	pathogenic	-0.165	Destabilizing	0.98	D	0.661	neutral	None	None	None	None	N
R/G	0.6301	likely_pathogenic	0.5722	pathogenic	-0.448	Destabilizing	0.917	D	0.5	neutral	N	0.460767769	None	None	N
R/H	0.2938	likely_benign	0.2734	benign	-0.857	Destabilizing	0.995	D	0.533	neutral	N	0.48781946	None	None	N
R/I	0.5143	ambiguous	0.4583	ambiguous	0.494	Stabilizing	0.945	D	0.661	neutral	None	None	None	None	N
R/K	0.1944	likely_benign	0.1828	benign	-0.304	Destabilizing	0.001	N	0.143	neutral	None	None	None	None	N
R/L	0.4611	ambiguous	0.4528	ambiguous	0.494	Stabilizing	0.821	D	0.5	neutral	N	0.391866207	None	None	N
R/M	0.6199	likely_pathogenic	0.5524	ambiguous	-0.04	Destabilizing	0.995	D	0.553	neutral	None	None	None	None	N
R/N	0.8683	likely_pathogenic	0.8587	pathogenic	-0.044	Destabilizing	0.953	D	0.505	neutral	None	None	None	None	N
R/P	0.8821	likely_pathogenic	0.8729	pathogenic	0.29	Stabilizing	0.987	D	0.635	neutral	N	0.48324036	None	None	N
R/Q	0.1926	likely_benign	0.177	benign	-0.111	Destabilizing	0.937	D	0.538	neutral	None	None	None	None	N
R/S	0.8259	likely_pathogenic	0.7916	pathogenic	-0.511	Destabilizing	0.917	D	0.537	neutral	N	0.403182066	None	None	N
R/T	0.6351	likely_pathogenic	0.5708	pathogenic	-0.244	Destabilizing	0.852	D	0.515	neutral	None	None	None	None	N
R/V	0.6215	likely_pathogenic	0.5805	pathogenic	0.29	Stabilizing	0.925	D	0.642	neutral	None	None	None	None	N
R/W	0.4263	ambiguous	0.3552	ambiguous	-0.069	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
R/Y	0.7239	likely_pathogenic	0.701	pathogenic	0.29	Stabilizing	0.98	D	0.631	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.