TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32173	96742;96743;96744	chr2:178543456;178543455;178543454	chr2:179408183;179408182;179408181
N2AB	30532	91819;91820;91821	chr2:178543456;178543455;178543454	chr2:179408183;179408182;179408181
N2A	29605	89038;89039;89040	chr2:178543456;178543455;178543454	chr2:179408183;179408182;179408181
N2B	23108	69547;69548;69549	chr2:178543456;178543455;178543454	chr2:179408183;179408182;179408181
Novex-1	23233	69922;69923;69924	chr2:178543456;178543455;178543454	chr2:179408183;179408182;179408181
Novex-2	23300	70123;70124;70125	chr2:178543456;178543455;178543454	chr2:179408183;179408182;179408181
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-122
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1359
• 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
T/I	rs770726467	0.15	None	N	0.213	0.139	0.403040389579	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
T/I	rs770726467	0.15	None	N	0.213	0.139	0.403040389579	gnomAD-4.0.0	3.42111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.79656E-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
T/A	0.0724	likely_benign	0.0666	benign	-0.931	Destabilizing	None	N	0.061	neutral	N	0.468578417	None	None	N
T/C	0.2918	likely_benign	0.2728	benign	-0.487	Destabilizing	0.356	N	0.417	neutral	None	None	None	None	N
T/D	0.4842	ambiguous	0.4187	ambiguous	-0.415	Destabilizing	0.072	N	0.448	neutral	None	None	None	None	N
T/E	0.3611	ambiguous	0.3191	benign	-0.305	Destabilizing	0.072	N	0.391	neutral	None	None	None	None	N
T/F	0.3147	likely_benign	0.2389	benign	-0.714	Destabilizing	0.214	N	0.458	neutral	None	None	None	None	N
T/G	0.1923	likely_benign	0.1708	benign	-1.287	Destabilizing	0.016	N	0.325	neutral	None	None	None	None	N
T/H	0.2764	likely_benign	0.2575	benign	-1.379	Destabilizing	0.628	D	0.417	neutral	None	None	None	None	N
T/I	0.1824	likely_benign	0.1575	benign	-0.034	Destabilizing	None	N	0.213	neutral	N	0.495458374	None	None	N
T/K	0.2518	likely_benign	0.2193	benign	-0.532	Destabilizing	0.072	N	0.392	neutral	None	None	None	None	N
T/L	0.1145	likely_benign	0.0966	benign	-0.034	Destabilizing	None	N	0.131	neutral	None	None	None	None	N
T/M	0.0886	likely_benign	0.0783	benign	0.014	Stabilizing	0.002	N	0.227	neutral	None	None	None	None	N
T/N	0.1103	likely_benign	0.1051	benign	-0.836	Destabilizing	0.055	N	0.39	neutral	N	0.434236557	None	None	N
T/P	0.6895	likely_pathogenic	0.6331	pathogenic	-0.3	Destabilizing	0.055	N	0.464	neutral	N	0.490244551	None	None	N
T/Q	0.2034	likely_benign	0.195	benign	-0.763	Destabilizing	0.214	N	0.454	neutral	None	None	None	None	N
T/R	0.2313	likely_benign	0.1948	benign	-0.511	Destabilizing	0.214	N	0.459	neutral	None	None	None	None	N
T/S	0.0932	likely_benign	0.0899	benign	-1.143	Destabilizing	0.002	N	0.151	neutral	N	0.457091987	None	None	N
T/V	0.1203	likely_benign	0.1074	benign	-0.3	Destabilizing	None	N	0.058	neutral	None	None	None	None	N
T/W	0.6749	likely_pathogenic	0.6036	pathogenic	-0.757	Destabilizing	0.864	D	0.419	neutral	None	None	None	None	N
T/Y	0.3332	likely_benign	0.2923	benign	-0.445	Destabilizing	0.356	N	0.457	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.