TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8615	26068;26069;26070	chr2:178715571;178715570;178715569	chr2:179580298;179580297;179580296
N2AB	8298	25117;25118;25119	chr2:178715571;178715570;178715569	chr2:179580298;179580297;179580296
N2A	7371	22336;22337;22338	chr2:178715571;178715570;178715569	chr2:179580298;179580297;179580296
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-71
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.7562
• 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
E/D	rs758944073	0.148	0.001	N	0.147	0.139	0.0666544352282	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
E/D	rs758944073	0.148	0.001	N	0.147	0.139	0.0666544352282	gnomAD-4.0.0	6.84269E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87308E-05	0	0	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
E/A	0.1246	likely_benign	0.1248	benign	-0.364	Destabilizing	0.789	D	0.481	neutral	N	0.509640314	None	None	N
E/C	0.8328	likely_pathogenic	0.8278	pathogenic	0.066	Stabilizing	0.998	D	0.545	neutral	None	None	None	None	N
E/D	0.1057	likely_benign	0.1017	benign	-0.179	Destabilizing	0.001	N	0.147	neutral	N	0.500058039	None	None	N
E/F	0.6921	likely_pathogenic	0.6842	pathogenic	-0.34	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	N
E/G	0.1392	likely_benign	0.1392	benign	-0.524	Destabilizing	0.926	D	0.48	neutral	N	0.472229888	None	None	N
E/H	0.3907	ambiguous	0.3821	ambiguous	-0.053	Destabilizing	0.993	D	0.476	neutral	None	None	None	None	N
E/I	0.3708	ambiguous	0.3749	ambiguous	0.011	Stabilizing	0.938	D	0.527	neutral	None	None	None	None	N
E/K	0.1198	likely_benign	0.1218	benign	0.454	Stabilizing	0.874	D	0.518	neutral	N	0.468938205	None	None	N
E/L	0.3582	ambiguous	0.3549	ambiguous	0.011	Stabilizing	0.811	D	0.453	neutral	None	None	None	None	N
E/M	0.4168	ambiguous	0.4193	ambiguous	0.16	Stabilizing	0.984	D	0.509	neutral	None	None	None	None	N
E/N	0.2226	likely_benign	0.2173	benign	0.161	Stabilizing	0.667	D	0.495	neutral	None	None	None	None	N
E/P	0.7005	likely_pathogenic	0.6613	pathogenic	-0.095	Destabilizing	0.933	D	0.46	neutral	None	None	None	None	N
E/Q	0.1324	likely_benign	0.1314	benign	0.191	Stabilizing	0.91	D	0.491	neutral	N	0.468293095	None	None	N
E/R	0.2125	likely_benign	0.2112	benign	0.582	Stabilizing	0.985	D	0.467	neutral	None	None	None	None	N
E/S	0.1626	likely_benign	0.1596	benign	0.01	Stabilizing	0.713	D	0.477	neutral	None	None	None	None	N
E/T	0.1852	likely_benign	0.1829	benign	0.148	Stabilizing	0.084	N	0.236	neutral	None	None	None	None	N
E/V	0.2279	likely_benign	0.2331	benign	-0.095	Destabilizing	0.698	D	0.447	neutral	N	0.491285649	None	None	N
E/W	0.8129	likely_pathogenic	0.8008	pathogenic	-0.219	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/Y	0.5714	likely_pathogenic	0.5626	ambiguous	-0.106	Destabilizing	0.998	D	0.519	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.