TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14134	42625;42626;42627	chr2:178634381;178634380;178634379	chr2:179499108;179499107;179499106
N2AB	12493	37702;37703;37704	chr2:178634381;178634380;178634379	chr2:179499108;179499107;179499106
N2A	11566	34921;34922;34923	chr2:178634381;178634380;178634379	chr2:179499108;179499107;179499106
N2B	5069	15430;15431;15432	chr2:178634381;178634380;178634379	chr2:179499108;179499107;179499106
Novex-1	5194	15805;15806;15807	chr2:178634381;178634380;178634379	chr2:179499108;179499107;179499106
Novex-2	5261	16006;16007;16008	chr2:178634381;178634380;178634379	chr2:179499108;179499107;179499106
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Ig-91
• Domain position: 81
• Structural Position: 173
• Q(SASA): 0.6118
• Predicted PPI site: I

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/P	rs764083952	0.067	0.232	N	0.579	0.135	0.188950314367	gnomAD-2.1.1	8.3E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.46E-05	None	0	9.1E-06	0
R/P	rs764083952	0.067	0.232	N	0.579	0.135	0.188950314367	gnomAD-4.0.0	2.06359E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.37074E-05	1.66572E-05
R/Q	rs764083952	0.224	None	N	0.215	0.04	0.0401082797425	gnomAD-2.1.1	2.94E-05	None	None	None	None	I	None	0	9.03E-05	None	0	1.58865E-04	None	0	None	0	1.6E-05	0
R/Q	rs764083952	0.224	None	N	0.215	0.04	0.0401082797425	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	1.94024E-04	None	0	0	1.47E-05	0	0
R/Q	rs764083952	0.224	None	N	0.215	0.04	0.0401082797425	gnomAD-4.0.0	1.86824E-05	None	None	None	None	I	None	1.34902E-05	5.20743E-05	None	3.4009E-05	6.72013E-05	None	0	1.65399E-04	1.52811E-05	1.12128E-05	3.21947E-05
R/W	rs753341792	-0.455	0.964	N	0.505	0.145	0.235038932564	gnomAD-2.1.1	4.12E-05	None	None	None	None	I	None	0	1.81796E-04	None	0	1.14312E-04	None	0	None	0	1.81E-05	0
R/W	rs753341792	-0.455	0.964	N	0.505	0.145	0.235038932564	gnomAD-3.1.2	4.61E-05	None	None	None	None	I	None	0	1.97031E-04	0	0	0	None	0	0	4.41E-05	2.07727E-04	0
R/W	rs753341792	-0.455	0.964	N	0.505	0.145	0.235038932564	gnomAD-4.0.0	2.67458E-05	None	None	None	None	I	None	0	1.54353E-04	None	0	4.47989E-05	None	0	0	2.54581E-05	2.22955E-05	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	0.3316	likely_benign	0.3016	benign	-0.903	Destabilizing	0.016	N	0.383	neutral	None	None	None	None	I
R/C	0.1828	likely_benign	0.1609	benign	-0.861	Destabilizing	0.864	D	0.503	neutral	None	None	None	None	I
R/D	0.5793	likely_pathogenic	0.5792	pathogenic	-0.02	Destabilizing	0.072	N	0.557	neutral	None	None	None	None	I
R/E	0.2741	likely_benign	0.2535	benign	0.142	Stabilizing	0.016	N	0.401	neutral	None	None	None	None	I
R/F	0.5453	ambiguous	0.539	ambiguous	-0.534	Destabilizing	0.628	D	0.537	neutral	None	None	None	None	I
R/G	0.2783	likely_benign	0.2784	benign	-1.239	Destabilizing	0.058	N	0.51	neutral	N	0.445593574	None	None	I
R/H	0.0886	likely_benign	0.0881	benign	-1.453	Destabilizing	0.214	N	0.591	neutral	None	None	None	None	I
R/I	0.2768	likely_benign	0.2516	benign	0.015	Stabilizing	0.356	N	0.553	neutral	None	None	None	None	I
R/K	0.0794	likely_benign	0.083	benign	-0.712	Destabilizing	None	N	0.209	neutral	None	None	None	None	I
R/L	0.2155	likely_benign	0.192	benign	0.015	Stabilizing	0.13	N	0.543	neutral	N	0.447575222	None	None	I
R/M	0.2594	likely_benign	0.245	benign	-0.475	Destabilizing	0.356	N	0.563	neutral	None	None	None	None	I
R/N	0.3608	ambiguous	0.3363	benign	-0.402	Destabilizing	0.072	N	0.519	neutral	None	None	None	None	I
R/P	0.7876	likely_pathogenic	0.7286	pathogenic	-0.271	Destabilizing	0.232	N	0.579	neutral	N	0.444888301	None	None	I
R/Q	0.0805	likely_benign	0.0715	benign	-0.453	Destabilizing	None	N	0.215	neutral	N	0.418362491	None	None	I
R/S	0.3258	likely_benign	0.313	benign	-1.189	Destabilizing	0.003	N	0.261	neutral	None	None	None	None	I
R/T	0.1626	likely_benign	0.1427	benign	-0.825	Destabilizing	0.038	N	0.555	neutral	None	None	None	None	I
R/V	0.31	likely_benign	0.294	benign	-0.271	Destabilizing	0.072	N	0.577	neutral	None	None	None	None	I
R/W	0.2301	likely_benign	0.2133	benign	-0.168	Destabilizing	0.964	D	0.505	neutral	N	0.452720368	None	None	I
R/Y	0.3585	ambiguous	0.3529	ambiguous	0.079	Stabilizing	0.356	N	0.555	neutral	None	None	None	None	I

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.