TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27168	81727;81728;81729	chr2:178564630;178564629;178564628	chr2:179429357;179429356;179429355
N2AB	25527	76804;76805;76806	chr2:178564630;178564629;178564628	chr2:179429357;179429356;179429355
N2A	24600	74023;74024;74025	chr2:178564630;178564629;178564628	chr2:179429357;179429356;179429355
N2B	18103	54532;54533;54534	chr2:178564630;178564629;178564628	chr2:179429357;179429356;179429355
Novex-1	18228	54907;54908;54909	chr2:178564630;178564629;178564628	chr2:179429357;179429356;179429355
Novex-2	18295	55108;55109;55110	chr2:178564630;178564629;178564628	chr2:179429357;179429356;179429355
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-85
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.6529
• 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	rs377616334	-0.292	1.0	N	0.893	0.311	None	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	2.06731E-04	5.67E-05	None	0	0	None	0	None	0	7.83E-06	0
R/C	rs377616334	-0.292	1.0	N	0.893	0.311	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs377616334	-0.292	1.0	N	0.893	0.311	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/C	rs377616334	-0.292	1.0	N	0.893	0.311	None	gnomAD-4.0.0	8.67691E-06	None	None	None	None	N	None	1.46682E-04	1.66756E-05	None	0	0	None	0	0	1.69536E-06	0	0
R/G	rs377616334	-0.722	1.0	N	0.674	0.282	0.471620082127	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
R/G	rs377616334	-0.722	1.0	N	0.674	0.282	0.471620082127	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	0	4.47487E-05	None	0	0	None	0	0	0	0	0
R/H	rs374160272	-1.029	1.0	N	0.823	0.424	None	gnomAD-2.1.1	3.93E-05	None	None	None	None	N	None	8.27E-05	2.83E-05	None	0	0	None	1.30753E-04	None	0	2.35E-05	1.40647E-04
R/H	rs374160272	-1.029	1.0	N	0.823	0.424	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	7.35E-05	0	0
R/H	rs374160272	-1.029	1.0	N	0.823	0.424	None	gnomAD-4.0.0	3.78077E-05	None	None	None	None	N	None	8.01218E-05	1.66795E-05	None	0	2.23324E-05	None	0	0	3.30593E-05	6.58776E-05	1.28115E-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	0.7741	likely_pathogenic	0.7349	pathogenic	-0.611	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
R/C	0.2784	likely_benign	0.2513	benign	-0.606	Destabilizing	1.0	D	0.893	deleterious	N	0.482543598	None	None	N
R/D	0.9671	likely_pathogenic	0.9604	pathogenic	-0.044	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
R/E	0.7347	likely_pathogenic	0.6955	pathogenic	0.042	Stabilizing	0.998	D	0.694	prob.delet.	None	None	None	None	N
R/F	0.8078	likely_pathogenic	0.7813	pathogenic	-0.699	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
R/G	0.7317	likely_pathogenic	0.6751	pathogenic	-0.864	Destabilizing	1.0	D	0.674	prob.neutral	N	0.468741303	None	None	N
R/H	0.2122	likely_benign	0.2025	benign	-1.183	Destabilizing	1.0	D	0.823	deleterious	N	0.508788155	None	None	N
R/I	0.4743	ambiguous	0.4411	ambiguous	0.044	Stabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
R/K	0.1597	likely_benign	0.158	benign	-0.626	Destabilizing	0.995	D	0.592	neutral	None	None	None	None	N
R/L	0.4761	ambiguous	0.4496	ambiguous	0.044	Stabilizing	1.0	D	0.674	prob.neutral	N	0.472935726	None	None	N
R/M	0.5446	ambiguous	0.5089	ambiguous	-0.206	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
R/N	0.9001	likely_pathogenic	0.8919	pathogenic	-0.114	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
R/P	0.9899	likely_pathogenic	0.9893	pathogenic	-0.154	Destabilizing	1.0	D	0.815	deleterious	N	0.514011558	None	None	N
R/Q	0.1756	likely_benign	0.1591	benign	-0.345	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
R/S	0.8536	likely_pathogenic	0.8288	pathogenic	-0.809	Destabilizing	1.0	D	0.767	deleterious	N	0.466032278	None	None	N
R/T	0.6031	likely_pathogenic	0.5819	pathogenic	-0.565	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
R/V	0.5485	ambiguous	0.5207	ambiguous	-0.154	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
R/W	0.3953	ambiguous	0.3344	benign	-0.468	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
R/Y	0.6773	likely_pathogenic	0.648	pathogenic	-0.126	Destabilizing	0.999	D	0.878	deleterious	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.