TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8682	26269;26270;26271	chr2:178715142;178715141;178715140	chr2:179579869;179579868;179579867
N2AB	8365	25318;25319;25320	chr2:178715142;178715141;178715140	chr2:179579869;179579868;179579867
N2A	7438	22537;22538;22539	chr2:178715142;178715141;178715140	chr2:179579869;179579868;179579867
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-72
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.3486
• 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/Q	None	None	0.031	N	0.111	0.068	0.221734844693	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.1662	likely_benign	0.1681	benign	-0.665	Destabilizing	0.427	N	0.272	neutral	N	0.474261957	None	None	N
E/C	0.8939	likely_pathogenic	0.889	pathogenic	-0.441	Destabilizing	0.995	D	0.466	neutral	None	None	None	None	N
E/D	0.2718	likely_benign	0.2936	benign	-0.569	Destabilizing	0.088	N	0.287	neutral	N	0.498176179	None	None	N
E/F	0.8085	likely_pathogenic	0.8102	pathogenic	-0.069	Destabilizing	0.969	D	0.427	neutral	None	None	None	None	N
E/G	0.2858	likely_benign	0.296	benign	-0.948	Destabilizing	0.857	D	0.323	neutral	N	0.494508329	None	None	N
E/H	0.6381	likely_pathogenic	0.6536	pathogenic	0.176	Stabilizing	0.022	N	0.159	neutral	None	None	None	None	N
E/I	0.3106	likely_benign	0.3055	benign	0.082	Stabilizing	0.937	D	0.44	neutral	None	None	None	None	N
E/K	0.2512	likely_benign	0.2744	benign	-0.041	Destabilizing	0.409	N	0.251	neutral	N	0.511740122	None	None	N
E/L	0.3392	likely_benign	0.3412	ambiguous	0.082	Stabilizing	0.675	D	0.38	neutral	None	None	None	None	N
E/M	0.4175	ambiguous	0.4122	ambiguous	0.148	Stabilizing	0.909	D	0.405	neutral	None	None	None	None	N
E/N	0.4363	ambiguous	0.4563	ambiguous	-0.659	Destabilizing	0.491	N	0.287	neutral	None	None	None	None	N
E/P	0.3333	likely_benign	0.3333	benign	-0.147	Destabilizing	None	N	0.166	neutral	None	None	None	None	N
E/Q	0.1476	likely_benign	0.1495	benign	-0.557	Destabilizing	0.031	N	0.111	neutral	N	0.448768866	None	None	N
E/R	0.4244	ambiguous	0.4487	ambiguous	0.377	Stabilizing	0.689	D	0.289	neutral	None	None	None	None	N
E/S	0.3241	likely_benign	0.3402	ambiguous	-0.847	Destabilizing	0.705	D	0.21	neutral	None	None	None	None	N
E/T	0.3208	likely_benign	0.3302	benign	-0.603	Destabilizing	0.768	D	0.281	neutral	None	None	None	None	N
E/V	0.1928	likely_benign	0.1901	benign	-0.147	Destabilizing	0.527	D	0.351	neutral	N	0.509433323	None	None	N
E/W	0.9488	likely_pathogenic	0.95	pathogenic	0.244	Stabilizing	0.999	D	0.49	neutral	None	None	None	None	N
E/Y	0.7359	likely_pathogenic	0.7409	pathogenic	0.207	Stabilizing	0.977	D	0.407	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.