TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16235	48928;48929;48930	chr2:178614904;178614903;178614902	chr2:179479631;179479630;179479629
N2AB	14594	44005;44006;44007	chr2:178614904;178614903;178614902	chr2:179479631;179479630;179479629
N2A	13667	41224;41225;41226	chr2:178614904;178614903;178614902	chr2:179479631;179479630;179479629
N2B	7170	21733;21734;21735	chr2:178614904;178614903;178614902	chr2:179479631;179479630;179479629
Novex-1	7295	22108;22109;22110	chr2:178614904;178614903;178614902	chr2:179479631;179479630;179479629
Novex-2	7362	22309;22310;22311	chr2:178614904;178614903;178614902	chr2:179479631;179479630;179479629
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: Fn3-5
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.5986
• 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
Q/L	None	None	None	N	0.199	0.184	0.0716867268079	gnomAD-4.0.0	3.32415E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.96584E-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	0.159	likely_benign	0.1623	benign	-0.149	Destabilizing	0.004	N	0.277	neutral	None	None	None	None	I
Q/C	0.3725	ambiguous	0.3599	ambiguous	0.065	Stabilizing	0.497	N	0.511	neutral	None	None	None	None	I
Q/D	0.5938	likely_pathogenic	0.5912	pathogenic	-0.071	Destabilizing	0.044	N	0.323	neutral	None	None	None	None	I
Q/E	0.1384	likely_benign	0.1324	benign	-0.12	Destabilizing	0.014	N	0.258	neutral	N	0.430053512	None	None	I
Q/F	0.3937	ambiguous	0.3781	ambiguous	-0.464	Destabilizing	0.022	N	0.533	neutral	None	None	None	None	I
Q/G	0.3313	likely_benign	0.3352	benign	-0.291	Destabilizing	0.018	N	0.482	neutral	None	None	None	None	I
Q/H	0.1821	likely_benign	0.1903	benign	-0.127	Destabilizing	None	N	0.141	neutral	N	0.449835862	None	None	I
Q/I	0.1999	likely_benign	0.1918	benign	0.13	Stabilizing	None	N	0.227	neutral	None	None	None	None	I
Q/K	0.1467	likely_benign	0.1467	benign	0.056	Stabilizing	0.014	N	0.281	neutral	N	0.431184991	None	None	I
Q/L	0.0596	likely_benign	0.0636	benign	0.13	Stabilizing	None	N	0.199	neutral	N	0.373717017	None	None	I
Q/M	0.1601	likely_benign	0.1815	benign	0.259	Stabilizing	None	N	0.119	neutral	None	None	None	None	I
Q/N	0.3143	likely_benign	0.3096	benign	-0.221	Destabilizing	0.044	N	0.333	neutral	None	None	None	None	I
Q/P	0.5728	likely_pathogenic	0.5173	ambiguous	0.063	Stabilizing	0.175	N	0.485	neutral	N	0.478860319	None	None	I
Q/R	0.1552	likely_benign	0.144	benign	0.257	Stabilizing	0.014	N	0.347	neutral	N	0.435730849	None	None	I
Q/S	0.245	likely_benign	0.2469	benign	-0.205	Destabilizing	0.018	N	0.269	neutral	None	None	None	None	I
Q/T	0.2293	likely_benign	0.223	benign	-0.116	Destabilizing	0.018	N	0.407	neutral	None	None	None	None	I
Q/V	0.1261	likely_benign	0.1304	benign	0.063	Stabilizing	0.001	N	0.363	neutral	None	None	None	None	I
Q/W	0.4719	ambiguous	0.4489	ambiguous	-0.487	Destabilizing	0.788	D	0.504	neutral	None	None	None	None	I
Q/Y	0.314	likely_benign	0.2962	benign	-0.214	Destabilizing	0.022	N	0.507	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.