TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23793	71602;71603;71604	chr2:178574755;178574754;178574753	chr2:179439482;179439481;179439480
N2AB	22152	66679;66680;66681	chr2:178574755;178574754;178574753	chr2:179439482;179439481;179439480
N2A	21225	63898;63899;63900	chr2:178574755;178574754;178574753	chr2:179439482;179439481;179439480
N2B	14728	44407;44408;44409	chr2:178574755;178574754;178574753	chr2:179439482;179439481;179439480
Novex-1	14853	44782;44783;44784	chr2:178574755;178574754;178574753	chr2:179439482;179439481;179439480
Novex-2	14920	44983;44984;44985	chr2:178574755;178574754;178574753	chr2:179439482;179439481;179439480
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: Fn3-60
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4883
• 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/A	None	None	0.349	N	0.401	0.131	0.151104730317	gnomAD-4.0.0	1.36947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9997E-07	0	1.65826E-05
T/S	rs1709465876	None	0.722	N	0.403	0.151	0.195762928549	gnomAD-4.0.0	1.36947E-06	None	None	None	None	N	None	5.97872E-05	0	None	0	0	None	0	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
T/A	0.0795	likely_benign	0.0777	benign	-0.968	Destabilizing	0.349	N	0.401	neutral	N	0.462220087	None	None	N
T/C	0.4501	ambiguous	0.4348	ambiguous	-0.538	Destabilizing	0.996	D	0.464	neutral	None	None	None	None	N
T/D	0.5874	likely_pathogenic	0.5709	pathogenic	-0.161	Destabilizing	0.775	D	0.392	neutral	None	None	None	None	N
T/E	0.4113	ambiguous	0.3944	ambiguous	-0.195	Destabilizing	0.775	D	0.417	neutral	None	None	None	None	N
T/F	0.4565	ambiguous	0.4431	ambiguous	-1.259	Destabilizing	0.987	D	0.537	neutral	None	None	None	None	N
T/G	0.2973	likely_benign	0.2841	benign	-1.168	Destabilizing	0.011	N	0.236	neutral	None	None	None	None	N
T/H	0.3412	ambiguous	0.3207	benign	-1.475	Destabilizing	0.996	D	0.531	neutral	None	None	None	None	N
T/I	0.2967	likely_benign	0.2804	benign	-0.535	Destabilizing	0.949	D	0.429	neutral	N	0.505397648	None	None	N
T/K	0.2372	likely_benign	0.2287	benign	-0.696	Destabilizing	0.044	N	0.249	neutral	None	None	None	None	N
T/L	0.1545	likely_benign	0.1463	benign	-0.535	Destabilizing	0.775	D	0.421	neutral	None	None	None	None	N
T/M	0.1082	likely_benign	0.1027	benign	-0.073	Destabilizing	0.996	D	0.453	neutral	None	None	None	None	N
T/N	0.1814	likely_benign	0.1745	benign	-0.559	Destabilizing	0.901	D	0.422	neutral	N	0.429283736	None	None	N
T/P	0.0995	likely_benign	0.09	benign	-0.65	Destabilizing	0.008	N	0.243	neutral	N	0.381553213	None	None	N
T/Q	0.2578	likely_benign	0.2418	benign	-0.825	Destabilizing	0.923	D	0.439	neutral	None	None	None	None	N
T/R	0.2033	likely_benign	0.1976	benign	-0.39	Destabilizing	0.858	D	0.417	neutral	None	None	None	None	N
T/S	0.1349	likely_benign	0.1334	benign	-0.87	Destabilizing	0.722	D	0.403	neutral	N	0.465473823	None	None	N
T/V	0.1803	likely_benign	0.1753	benign	-0.65	Destabilizing	0.775	D	0.426	neutral	None	None	None	None	N
T/W	0.7738	likely_pathogenic	0.7572	pathogenic	-1.134	Destabilizing	0.996	D	0.582	neutral	None	None	None	None	N
T/Y	0.4673	ambiguous	0.4428	ambiguous	-0.915	Destabilizing	0.987	D	0.533	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.