TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23602	71029;71030;71031	chr2:178575328;178575327;178575326	chr2:179440055;179440054;179440053
N2AB	21961	66106;66107;66108	chr2:178575328;178575327;178575326	chr2:179440055;179440054;179440053
N2A	21034	63325;63326;63327	chr2:178575328;178575327;178575326	chr2:179440055;179440054;179440053
N2B	14537	43834;43835;43836	chr2:178575328;178575327;178575326	chr2:179440055;179440054;179440053
Novex-1	14662	44209;44210;44211	chr2:178575328;178575327;178575326	chr2:179440055;179440054;179440053
Novex-2	14729	44410;44411;44412	chr2:178575328;178575327;178575326	chr2:179440055;179440054;179440053
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-59
• Domain position: 71
• Structural Position: 105
• Q(SASA): 0.1573
• 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/S	None	None	0.822	N	0.663	0.203	0.251116650651	gnomAD-4.0.0	1.59192E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41429E-04	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	0.0901	likely_benign	0.0837	benign	-1.345	Destabilizing	0.489	N	0.66	neutral	N	0.471229146	None	None	N
T/C	0.2997	likely_benign	0.2774	benign	-0.904	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	N
T/D	0.4701	ambiguous	0.4267	ambiguous	-1.911	Destabilizing	0.978	D	0.736	prob.delet.	None	None	None	None	N
T/E	0.3768	ambiguous	0.3343	benign	-1.666	Destabilizing	0.956	D	0.753	deleterious	None	None	None	None	N
T/F	0.1925	likely_benign	0.1758	benign	-0.749	Destabilizing	0.978	D	0.767	deleterious	None	None	None	None	N
T/G	0.3037	likely_benign	0.2742	benign	-1.768	Destabilizing	0.86	D	0.726	prob.delet.	None	None	None	None	N
T/H	0.206	likely_benign	0.1884	benign	-1.722	Destabilizing	0.994	D	0.76	deleterious	None	None	None	None	N
T/I	0.0874	likely_benign	0.0841	benign	-0.208	Destabilizing	0.698	D	0.728	prob.delet.	N	0.479560628	None	None	N
T/K	0.2161	likely_benign	0.1944	benign	-0.607	Destabilizing	0.754	D	0.732	prob.delet.	None	None	None	None	N
T/L	0.0662	likely_benign	0.0633	benign	-0.208	Destabilizing	0.754	D	0.706	prob.neutral	None	None	None	None	N
T/M	0.0821	likely_benign	0.0786	benign	-0.404	Destabilizing	0.978	D	0.762	deleterious	None	None	None	None	N
T/N	0.1288	likely_benign	0.1215	benign	-1.382	Destabilizing	0.942	D	0.705	prob.neutral	N	0.48338758	None	None	N
T/P	0.6105	likely_pathogenic	0.5254	ambiguous	-0.56	Destabilizing	0.99	D	0.763	deleterious	N	0.49475664	None	None	N
T/Q	0.2386	likely_benign	0.2143	benign	-1.03	Destabilizing	0.956	D	0.76	deleterious	None	None	None	None	N
T/R	0.1588	likely_benign	0.1433	benign	-0.924	Destabilizing	0.043	N	0.508	neutral	None	None	None	None	N
T/S	0.1133	likely_benign	0.1059	benign	-1.572	Destabilizing	0.822	D	0.663	neutral	N	0.432574758	None	None	N
T/V	0.0813	likely_benign	0.0792	benign	-0.56	Destabilizing	0.019	N	0.357	neutral	None	None	None	None	N
T/W	0.5527	ambiguous	0.5052	ambiguous	-1.017	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
T/Y	0.2231	likely_benign	0.2059	benign	-0.63	Destabilizing	0.993	D	0.779	deleterious	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.