TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8646	26161;26162;26163	chr2:178715250;178715249;178715248	chr2:179579977;179579976;179579975
N2AB	8329	25210;25211;25212	chr2:178715250;178715249;178715248	chr2:179579977;179579976;179579975
N2A	7402	22429;22430;22431	chr2:178715250;178715249;178715248	chr2:179579977;179579976;179579975
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-72
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.571
• 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/C	rs72648987	-0.197	0.001	N	0.207	0.084	None	gnomAD-2.1.1	1.65369E-02	None	None	None	None	I	None	3.87565E-03	1.41441E-02	None	1.25052E-02	1.04998E-04	None	1.49592E-02	None	2.11205E-02	2.17043E-02	1.96136E-02
R/C	rs72648987	-0.197	0.001	N	0.207	0.084	None	gnomAD-3.1.2	1.65713E-02	None	None	None	None	I	None	4.66116E-03	2.50492E-02	3.28947E-03	1.09447E-02	1.9305E-04	None	2.10576E-02	1.89873E-02	2.28282E-02	1.66182E-02	1.96737E-02
R/C	rs72648987	-0.197	0.001	N	0.207	0.084	None	1000 genomes	9.38498E-03	None	None	None	None	I	None	0	1.59E-02	None	None	0	2.58E-02	None	None	None	1.02E-02	None
R/C	rs72648987	-0.197	0.001	N	0.207	0.084	None	gnomAD-4.0.0	1.88575E-02	None	None	None	None	I	None	4.02813E-03	1.75393E-02	None	1.19703E-02	8.94334E-05	None	2.25869E-02	1.83596E-02	2.0923E-02	1.49913E-02	1.7455E-02
R/H	rs144587343	-0.836	None	N	0.142	0.06	None	gnomAD-2.1.1	7.37E-05	None	None	None	None	I	None	4.16458E-04	2.99E-05	None	0	0	None	1.41064E-04	None	0	3.2E-05	1.46284E-04
R/H	rs144587343	-0.836	None	N	0.142	0.06	None	gnomAD-3.1.2	1.64619E-04	None	None	None	None	I	None	3.87203E-04	1.3113E-04	0	0	0	None	0	0	7.36E-05	2.07469E-04	4.79846E-04
R/H	rs144587343	-0.836	None	N	0.142	0.06	None	1000 genomes	3.99361E-04	None	None	None	None	I	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
R/H	rs144587343	-0.836	None	N	0.142	0.06	None	gnomAD-4.0.0	1.07994E-04	None	None	None	None	I	None	4.31034E-04	6.88373E-05	None	0	2.23444E-05	None	0	0	1.03867E-04	7.88555E-05	1.13129E-04
R/L	rs144587343	None	None	N	0.089	0.078	0.144782658237	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
R/L	rs144587343	None	None	N	0.089	0.078	0.144782658237	gnomAD-4.0.0	1.24858E-06	None	None	None	None	I	None	0	1.72153E-05	None	0	0	None	0	0	8.51362E-07	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	0.1773	likely_benign	0.1593	benign	-0.061	Destabilizing	0.004	N	0.182	neutral	None	None	None	None	I
R/C	0.0884	likely_benign	0.0988	benign	-0.121	Destabilizing	0.001	N	0.207	neutral	N	0.469599059	None	None	I
R/D	0.3789	ambiguous	0.3853	ambiguous	-0.073	Destabilizing	0.02	N	0.392	neutral	None	None	None	None	I
R/E	0.1947	likely_benign	0.1931	benign	0.011	Stabilizing	0.003	N	0.185	neutral	None	None	None	None	I
R/F	0.2457	likely_benign	0.2391	benign	-0.134	Destabilizing	0.008	N	0.443	neutral	None	None	None	None	I
R/G	0.121	likely_benign	0.1131	benign	-0.3	Destabilizing	0.016	N	0.25	neutral	N	0.463499806	None	None	I
R/H	0.0706	likely_benign	0.0741	benign	-0.807	Destabilizing	None	N	0.142	neutral	N	0.4694257	None	None	I
R/I	0.1022	likely_benign	0.1012	benign	0.547	Stabilizing	None	N	0.187	neutral	None	None	None	None	I
R/K	0.0846	likely_benign	0.0844	benign	-0.156	Destabilizing	0.001	N	0.225	neutral	None	None	None	None	I
R/L	0.1017	likely_benign	0.1053	benign	0.547	Stabilizing	None	N	0.089	neutral	N	0.400891122	None	None	I
R/M	0.1398	likely_benign	0.135	benign	0.086	Stabilizing	0.056	N	0.298	neutral	None	None	None	None	I
R/N	0.2561	likely_benign	0.2553	benign	0.165	Stabilizing	0.02	N	0.217	neutral	None	None	None	None	I
R/P	0.5788	likely_pathogenic	0.5899	pathogenic	0.366	Stabilizing	0.072	N	0.447	neutral	N	0.482637353	None	None	I
R/Q	0.0716	likely_benign	0.074	benign	0.064	Stabilizing	0.029	N	0.31	neutral	None	None	None	None	I
R/S	0.1713	likely_benign	0.156	benign	-0.23	Destabilizing	None	N	0.121	neutral	N	0.404702218	None	None	I
R/T	0.1008	likely_benign	0.0908	benign	0.002	Stabilizing	None	N	0.083	neutral	None	None	None	None	I
R/V	0.1491	likely_benign	0.1442	benign	0.366	Stabilizing	None	N	0.153	neutral	None	None	None	None	I
R/W	0.0955	likely_benign	0.0982	benign	-0.102	Destabilizing	0.618	D	0.287	neutral	None	None	None	None	I
R/Y	0.1651	likely_benign	0.1738	benign	0.276	Stabilizing	None	N	0.157	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.