TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15789	47590;47591;47592	chr2:178617986;178617985;178617984	chr2:179482713;179482712;179482711
N2AB	14148	42667;42668;42669	chr2:178617986;178617985;178617984	chr2:179482713;179482712;179482711
N2A	13221	39886;39887;39888	chr2:178617986;178617985;178617984	chr2:179482713;179482712;179482711
N2B	6724	20395;20396;20397	chr2:178617986;178617985;178617984	chr2:179482713;179482712;179482711
Novex-1	6849	20770;20771;20772	chr2:178617986;178617985;178617984	chr2:179482713;179482712;179482711
Novex-2	6916	20971;20972;20973	chr2:178617986;178617985;178617984	chr2:179482713;179482712;179482711
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-2
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7509
• 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
E/A	None	None	0.201	N	0.425	0.112	0.236890367714	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/D	None	None	0.549	N	0.361	0.1	0.211220785272	gnomAD-4.0.0	1.59351E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02957E-05
E/K	None	None	0.549	N	0.379	0.161	0.289474373501	gnomAD-4.0.0	1.09541E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.43983E-05	0	0
E/Q	rs755290030	0.29	0.712	N	0.408	0.122	0.227260227426	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs755290030	0.29	0.712	N	0.408	0.122	0.227260227426	gnomAD-4.0.0	6.8463E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15972E-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
E/A	0.1005	likely_benign	0.1085	benign	-0.278	Destabilizing	0.201	N	0.425	neutral	N	0.48430244	None	None	I
E/C	0.7625	likely_pathogenic	0.7582	pathogenic	-0.044	Destabilizing	0.992	D	0.45	neutral	None	None	None	None	I
E/D	0.1186	likely_benign	0.1077	benign	-0.252	Destabilizing	0.549	D	0.361	neutral	N	0.482529858	None	None	I
E/F	0.6903	likely_pathogenic	0.678	pathogenic	-0.197	Destabilizing	0.85	D	0.448	neutral	None	None	None	None	I
E/G	0.1485	likely_benign	0.1631	benign	-0.468	Destabilizing	0.549	D	0.446	neutral	N	0.506169014	None	None	I
E/H	0.3813	ambiguous	0.3872	ambiguous	0.073	Stabilizing	0.972	D	0.39	neutral	None	None	None	None	I
E/I	0.2835	likely_benign	0.2876	benign	0.183	Stabilizing	0.217	N	0.433	neutral	None	None	None	None	I
E/K	0.1018	likely_benign	0.1258	benign	0.288	Stabilizing	0.549	D	0.379	neutral	N	0.484790526	None	None	I
E/L	0.3027	likely_benign	0.3125	benign	0.183	Stabilizing	0.447	N	0.485	neutral	None	None	None	None	I
E/M	0.3723	ambiguous	0.3933	ambiguous	0.201	Stabilizing	0.92	D	0.435	neutral	None	None	None	None	I
E/N	0.2032	likely_benign	0.2027	benign	0.07	Stabilizing	0.92	D	0.403	neutral	None	None	None	None	I
E/P	0.1803	likely_benign	0.1956	benign	0.049	Stabilizing	0.001	N	0.148	neutral	None	None	None	None	I
E/Q	0.114	likely_benign	0.1235	benign	0.101	Stabilizing	0.712	D	0.408	neutral	N	0.480934459	None	None	I
E/R	0.1778	likely_benign	0.2003	benign	0.511	Stabilizing	0.92	D	0.41	neutral	None	None	None	None	I
E/S	0.1497	likely_benign	0.1485	benign	-0.121	Destabilizing	0.617	D	0.378	neutral	None	None	None	None	I
E/T	0.162	likely_benign	0.1716	benign	0.03	Stabilizing	0.617	D	0.429	neutral	None	None	None	None	I
E/V	0.1644	likely_benign	0.1726	benign	0.049	Stabilizing	0.004	N	0.251	neutral	N	0.483172183	None	None	I
E/W	0.8489	likely_pathogenic	0.871	pathogenic	-0.078	Destabilizing	0.992	D	0.563	neutral	None	None	None	None	I
E/Y	0.5621	ambiguous	0.5767	pathogenic	0.038	Stabilizing	0.92	D	0.451	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.