TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16438	49537;49538;49539	chr2:178614085;178614084;178614083	chr2:179478812;179478811;179478810
N2AB	14797	44614;44615;44616	chr2:178614085;178614084;178614083	chr2:179478812;179478811;179478810
N2A	13870	41833;41834;41835	chr2:178614085;178614084;178614083	chr2:179478812;179478811;179478810
N2B	7373	22342;22343;22344	chr2:178614085;178614084;178614083	chr2:179478812;179478811;179478810
Novex-1	7498	22717;22718;22719	chr2:178614085;178614084;178614083	chr2:179478812;179478811;179478810
Novex-2	7565	22918;22919;22920	chr2:178614085;178614084;178614083	chr2:179478812;179478811;179478810
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: Fn3-6
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.3898
• 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/L	None	None	0.915	N	0.595	0.283	0.451599300725	gnomAD-4.0.0	1.59403E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43382E-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
Q/A	0.1953	likely_benign	0.1697	benign	-0.611	Destabilizing	0.745	D	0.457	neutral	None	None	None	None	N
Q/C	0.6416	likely_pathogenic	0.5845	pathogenic	-0.137	Destabilizing	0.998	D	0.691	prob.delet.	None	None	None	None	N
Q/D	0.4244	ambiguous	0.3637	ambiguous	-0.154	Destabilizing	0.594	D	0.472	neutral	None	None	None	None	N
Q/E	0.0687	likely_benign	0.0667	benign	-0.035	Destabilizing	0.01	N	0.177	neutral	N	0.347960354	None	None	N
Q/F	0.6099	likely_pathogenic	0.573	pathogenic	-0.41	Destabilizing	0.994	D	0.662	prob.neutral	None	None	None	None	N
Q/G	0.4447	ambiguous	0.3855	ambiguous	-0.935	Destabilizing	0.935	D	0.623	neutral	None	None	None	None	N
Q/H	0.2869	likely_benign	0.2622	benign	-0.371	Destabilizing	0.991	D	0.483	neutral	N	0.495348828	None	None	N
Q/I	0.226	likely_benign	0.2051	benign	0.213	Stabilizing	0.994	D	0.693	prob.delet.	None	None	None	None	N
Q/K	0.1428	likely_benign	0.126	benign	-0.032	Destabilizing	0.688	D	0.509	neutral	N	0.475690196	None	None	N
Q/L	0.1097	likely_benign	0.0994	benign	0.213	Stabilizing	0.915	D	0.595	neutral	N	0.44735848	None	None	N
Q/M	0.2265	likely_benign	0.211	benign	0.258	Stabilizing	0.994	D	0.496	neutral	None	None	None	None	N
Q/N	0.2939	likely_benign	0.2747	benign	-0.703	Destabilizing	0.935	D	0.399	neutral	None	None	None	None	N
Q/P	0.2256	likely_benign	0.189	benign	-0.033	Destabilizing	0.971	D	0.578	neutral	N	0.44961159	None	None	N
Q/R	0.1934	likely_benign	0.1681	benign	0.114	Stabilizing	0.842	D	0.441	neutral	N	0.489544762	None	None	N
Q/S	0.2219	likely_benign	0.2083	benign	-0.861	Destabilizing	0.745	D	0.432	neutral	None	None	None	None	N
Q/T	0.1272	likely_benign	0.1182	benign	-0.544	Destabilizing	0.935	D	0.5	neutral	None	None	None	None	N
Q/V	0.1369	likely_benign	0.1216	benign	-0.033	Destabilizing	0.935	D	0.599	neutral	None	None	None	None	N
Q/W	0.6852	likely_pathogenic	0.6253	pathogenic	-0.309	Destabilizing	0.998	D	0.688	prob.delet.	None	None	None	None	N
Q/Y	0.4922	ambiguous	0.4482	ambiguous	-0.039	Destabilizing	0.994	D	0.568	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.