TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16985	51178;51179;51180	chr2:178611176;178611175;178611174	chr2:179475903;179475902;179475901
N2AB	15344	46255;46256;46257	chr2:178611176;178611175;178611174	chr2:179475903;179475902;179475901
N2A	14417	43474;43475;43476	chr2:178611176;178611175;178611174	chr2:179475903;179475902;179475901
N2B	7920	23983;23984;23985	chr2:178611176;178611175;178611174	chr2:179475903;179475902;179475901
Novex-1	8045	24358;24359;24360	chr2:178611176;178611175;178611174	chr2:179475903;179475902;179475901
Novex-2	8112	24559;24560;24561	chr2:178611176;178611175;178611174	chr2:179475903;179475902;179475901
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-111
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.3925
• 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
T/A	None	None	0.826	N	0.436	0.241	0.306377322295	gnomAD-4.0.0	2.73844E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59934E-06	0	0
T/I	rs116765281	0.028	0.996	D	0.567	0.372	None	gnomAD-2.1.1	5.73E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.25315E-04	0
T/I	rs116765281	0.028	0.996	D	0.567	0.372	None	gnomAD-3.1.2	4.61E-05	None	None	None	None	I	None	7.25E-05	0	0	0	0	None	0	0	5.89E-05	0	0
T/I	rs116765281	0.028	0.996	D	0.567	0.372	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
T/I	rs116765281	0.028	0.996	D	0.567	0.372	None	gnomAD-4.0.0	1.30214E-04	None	None	None	None	I	None	4.00267E-05	0	None	0	0	None	0	0	1.67904E-04	0	1.44194E-04
T/P	rs1301584675	None	0.996	D	0.563	0.522	0.453119318887	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
T/P	rs1301584675	None	0.996	D	0.563	0.522	0.453119318887	gnomAD-4.0.0	1.31619E-05	None	None	None	None	I	None	4.82882E-05	0	None	0	0	None	0	0	0	0	0
T/S	rs1301584675	None	0.826	N	0.447	0.186	0.212008924253	gnomAD-4.0.0	6.84609E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65832E-05

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	0.0684	likely_benign	0.0672	benign	-0.46	Destabilizing	0.826	D	0.436	neutral	N	0.511841424	None	None	I
T/C	0.3829	ambiguous	0.3861	ambiguous	-0.351	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	I
T/D	0.2999	likely_benign	0.3122	benign	-0.042	Destabilizing	0.969	D	0.507	neutral	None	None	None	None	I
T/E	0.2319	likely_benign	0.2309	benign	-0.094	Destabilizing	0.939	D	0.466	neutral	None	None	None	None	I
T/F	0.2187	likely_benign	0.2397	benign	-0.774	Destabilizing	0.997	D	0.606	neutral	None	None	None	None	I
T/G	0.2091	likely_benign	0.2127	benign	-0.642	Destabilizing	0.969	D	0.517	neutral	None	None	None	None	I
T/H	0.2002	likely_benign	0.213	benign	-0.939	Destabilizing	0.997	D	0.592	neutral	None	None	None	None	I
T/I	0.1203	likely_benign	0.1246	benign	-0.088	Destabilizing	0.996	D	0.567	neutral	D	0.542078347	None	None	I
T/K	0.1264	likely_benign	0.1377	benign	-0.603	Destabilizing	0.079	N	0.231	neutral	None	None	None	None	I
T/L	0.089	likely_benign	0.0926	benign	-0.088	Destabilizing	0.969	D	0.465	neutral	None	None	None	None	I
T/M	0.0894	likely_benign	0.085	benign	0.06	Stabilizing	0.997	D	0.543	neutral	None	None	None	None	I
T/N	0.1019	likely_benign	0.1046	benign	-0.421	Destabilizing	0.959	D	0.453	neutral	D	0.54055012	None	None	I
T/P	0.3401	ambiguous	0.3104	benign	-0.181	Destabilizing	0.996	D	0.563	neutral	D	0.585711886	None	None	I
T/Q	0.1765	likely_benign	0.1804	benign	-0.619	Destabilizing	0.982	D	0.547	neutral	None	None	None	None	I
T/R	0.1258	likely_benign	0.1325	benign	-0.317	Destabilizing	0.046	N	0.33	neutral	None	None	None	None	I
T/S	0.0953	likely_benign	0.0967	benign	-0.62	Destabilizing	0.826	D	0.447	neutral	N	0.492443505	None	None	I
T/V	0.098	likely_benign	0.1012	benign	-0.181	Destabilizing	0.969	D	0.406	neutral	None	None	None	None	I
T/W	0.5934	likely_pathogenic	0.596	pathogenic	-0.771	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	I
T/Y	0.2705	likely_benign	0.2771	benign	-0.515	Destabilizing	0.997	D	0.608	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.