TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23834	71725;71726;71727	chr2:178574632;178574631;178574630	chr2:179439359;179439358;179439357
N2AB	22193	66802;66803;66804	chr2:178574632;178574631;178574630	chr2:179439359;179439358;179439357
N2A	21266	64021;64022;64023	chr2:178574632;178574631;178574630	chr2:179439359;179439358;179439357
N2B	14769	44530;44531;44532	chr2:178574632;178574631;178574630	chr2:179439359;179439358;179439357
Novex-1	14894	44905;44906;44907	chr2:178574632;178574631;178574630	chr2:179439359;179439358;179439357
Novex-2	14961	45106;45107;45108	chr2:178574632;178574631;178574630	chr2:179439359;179439358;179439357
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-61
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5666
• 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
Q/P	rs757958768	0.26	0.784	N	0.573	0.269	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
Q/P	rs757958768	0.26	0.784	N	0.573	0.269	None	gnomAD-4.0.0	2.73818E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59916E-06	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
Q/A	0.1738	likely_benign	0.1671	benign	-0.259	Destabilizing	0.176	N	0.334	neutral	None	None	None	None	N
Q/C	0.3882	ambiguous	0.3815	ambiguous	0.207	Stabilizing	0.995	D	0.461	neutral	None	None	None	None	N
Q/D	0.3488	ambiguous	0.3201	benign	-0.005	Destabilizing	0.704	D	0.421	neutral	None	None	None	None	N
Q/E	0.0858	likely_benign	0.0826	benign	-0.021	Destabilizing	0.425	N	0.423	neutral	N	0.411218051	None	None	N
Q/F	0.3942	ambiguous	0.399	ambiguous	-0.372	Destabilizing	0.003	N	0.349	neutral	None	None	None	None	N
Q/G	0.2897	likely_benign	0.266	benign	-0.475	Destabilizing	0.495	N	0.437	neutral	None	None	None	None	N
Q/H	0.1246	likely_benign	0.1227	benign	-0.402	Destabilizing	0.975	D	0.498	neutral	N	0.496527449	None	None	N
Q/I	0.1917	likely_benign	0.19	benign	0.227	Stabilizing	0.543	D	0.473	neutral	None	None	None	None	N
Q/K	0.09	likely_benign	0.0854	benign	0.027	Stabilizing	0.425	N	0.445	neutral	N	0.422856409	None	None	N
Q/L	0.0907	likely_benign	0.0932	benign	0.227	Stabilizing	0.27	N	0.34	neutral	N	0.488121396	None	None	N
Q/M	0.2386	likely_benign	0.2353	benign	0.509	Stabilizing	0.944	D	0.477	neutral	None	None	None	None	N
Q/N	0.2433	likely_benign	0.2361	benign	-0.277	Destabilizing	0.704	D	0.413	neutral	None	None	None	None	N
Q/P	0.6286	likely_pathogenic	0.536	ambiguous	0.094	Stabilizing	0.784	D	0.573	neutral	N	0.48014465	None	None	N
Q/R	0.0917	likely_benign	0.0879	benign	0.16	Stabilizing	0.784	D	0.447	neutral	N	0.436479068	None	None	N
Q/S	0.1963	likely_benign	0.1872	benign	-0.291	Destabilizing	0.037	N	0.159	neutral	None	None	None	None	N
Q/T	0.1454	likely_benign	0.1401	benign	-0.145	Destabilizing	0.329	N	0.457	neutral	None	None	None	None	N
Q/V	0.1274	likely_benign	0.1251	benign	0.094	Stabilizing	0.013	N	0.285	neutral	None	None	None	None	N
Q/W	0.3608	ambiguous	0.3475	ambiguous	-0.322	Destabilizing	0.995	D	0.463	neutral	None	None	None	None	N
Q/Y	0.2586	likely_benign	0.2548	benign	-0.08	Destabilizing	0.543	D	0.489	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.