TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3363	10312;10313;10314	chr2:178764204;178764203;178764202	chr2:179628931;179628930;179628929
N2AB	3363	10312;10313;10314	chr2:178764204;178764203;178764202	chr2:179628931;179628930;179628929
N2A	3363	10312;10313;10314	chr2:178764204;178764203;178764202	chr2:179628931;179628930;179628929
N2B	3317	10174;10175;10176	chr2:178764204;178764203;178764202	chr2:179628931;179628930;179628929
Novex-1	3317	10174;10175;10176	chr2:178764204;178764203;178764202	chr2:179628931;179628930;179628929
Novex-2	3317	10174;10175;10176	chr2:178764204;178764203;178764202	chr2:179628931;179628930;179628929
Novex-3	3363	10312;10313;10314	chr2:178764204;178764203;178764202	chr2:179628931;179628930;179628929

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-24
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.5862
• 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	rs764030230	-0.128	0.002	D	0.503	0.389	0.514184785564	gnomAD-2.1.1	2.83E-05	None	None	None	None	N	None	0	1.41107E-04	None	0	0	None	0	None	0	2.32E-05	0
R/C	rs764030230	-0.128	0.002	D	0.503	0.389	0.514184785564	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	4.41E-05	0	0
R/C	rs764030230	-0.128	0.002	D	0.503	0.389	0.514184785564	gnomAD-4.0.0	1.30118E-05	None	None	None	None	N	None	0	1.16671E-04	None	0	0	None	0	0	1.10172E-05	0	1.60046E-05
R/G	None	None	0.13	D	0.543	0.452	0.543165868402	gnomAD-4.0.0	6.84086E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	0
R/H	rs148169214	-1.11	None	N	0.281	0.191	None	gnomAD-2.1.1	2.33473E-04	None	None	None	None	N	None	2.04278E-03	2.82E-05	None	0	2.50954E-04	None	3.27E-05	None	0	5.42E-05	1.38504E-04
R/H	rs148169214	-1.11	None	N	0.281	0.191	None	gnomAD-3.1.2	7.42737E-04	None	None	None	None	N	None	2.6063E-03	0	0	0	1.92678E-04	None	0	0	4.41E-05	0	4.77555E-04
R/H	rs148169214	-1.11	None	N	0.281	0.191	None	1000 genomes	7.98722E-04	None	None	None	None	N	None	3E-03	0	None	None	0	0	None	None	None	0	None
R/H	rs148169214	-1.11	None	N	0.281	0.191	None	gnomAD-4.0.0	1.52411E-04	None	None	None	None	N	None	2.47881E-03	1.66628E-05	None	0	4.45772E-05	None	0	1.64962E-04	3.64423E-05	3.29381E-05	1.5998E-04

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	0.2667	likely_benign	0.281	benign	-0.294	Destabilizing	0.016	N	0.519	neutral	None	None	None	None	N
R/C	0.1042	likely_benign	0.0894	benign	-0.144	Destabilizing	0.002	N	0.503	neutral	D	0.562333372	None	None	N
R/D	0.5286	ambiguous	0.544	ambiguous	0.099	Stabilizing	0.072	N	0.535	neutral	None	None	None	None	N
R/E	0.3114	likely_benign	0.3451	ambiguous	0.217	Stabilizing	0.016	N	0.573	neutral	None	None	None	None	N
R/F	0.3041	likely_benign	0.2771	benign	-0.104	Destabilizing	0.214	N	0.534	neutral	None	None	None	None	N
R/G	0.2171	likely_benign	0.2277	benign	-0.603	Destabilizing	0.13	N	0.543	neutral	D	0.655958947	None	None	N
R/H	0.0683	likely_benign	0.0664	benign	-1.081	Destabilizing	None	N	0.281	neutral	N	0.521472719	None	None	N
R/I	0.168	likely_benign	0.1588	benign	0.527	Stabilizing	0.214	N	0.541	neutral	None	None	None	None	N
R/K	0.1355	likely_benign	0.1483	benign	-0.332	Destabilizing	0.016	N	0.567	neutral	None	None	None	None	N
R/L	0.1451	likely_benign	0.1379	benign	0.527	Stabilizing	0.07	N	0.547	neutral	N	0.518718672	None	None	N
R/M	0.2849	likely_benign	0.2779	benign	0.105	Stabilizing	0.628	D	0.555	neutral	None	None	None	None	N
R/N	0.351	ambiguous	0.3574	ambiguous	0.189	Stabilizing	0.038	N	0.553	neutral	None	None	None	None	N
R/P	0.7455	likely_pathogenic	0.8019	pathogenic	0.276	Stabilizing	0.515	D	0.546	neutral	D	0.694157157	None	None	N
R/Q	0.0938	likely_benign	0.097	benign	0.081	Stabilizing	0.003	N	0.369	neutral	None	None	None	None	N
R/S	0.252	likely_benign	0.2776	benign	-0.384	Destabilizing	0.13	N	0.557	neutral	N	0.512267312	None	None	N
R/T	0.1643	likely_benign	0.1846	benign	-0.092	Destabilizing	0.072	N	0.555	neutral	None	None	None	None	N
R/V	0.2097	likely_benign	0.2029	benign	0.276	Stabilizing	0.072	N	0.531	neutral	None	None	None	None	N
R/W	0.1434	likely_benign	0.1312	benign	0.113	Stabilizing	0.864	D	0.515	neutral	None	None	None	None	N
R/Y	0.1982	likely_benign	0.1806	benign	0.425	Stabilizing	0.12	N	0.551	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.