TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33357	100294;100295;100296	chr2:178537040;178537039;178537038	chr2:179401767;179401766;179401765
N2AB	31716	95371;95372;95373	chr2:178537040;178537039;178537038	chr2:179401767;179401766;179401765
N2A	30789	92590;92591;92592	chr2:178537040;178537039;178537038	chr2:179401767;179401766;179401765
N2B	24292	73099;73100;73101	chr2:178537040;178537039;178537038	chr2:179401767;179401766;179401765
Novex-1	24417	73474;73475;73476	chr2:178537040;178537039;178537038	chr2:179401767;179401766;179401765
Novex-2	24484	73675;73676;73677	chr2:178537040;178537039;178537038	chr2:179401767;179401766;179401765
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-130
• Domain position: 68
• Structural Position: 98
• Q(SASA): 0.5091
• 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/I	None	None	0.026	N	0.229	0.148	0.220303561663	gnomAD-4.0.0	6.84498E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16074E-05	0
T/K	None	None	0.968	N	0.521	0.203	0.284539287134	gnomAD-4.0.0	6.16048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09705E-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
T/A	0.1035	likely_benign	0.0839	benign	-0.958	Destabilizing	0.896	D	0.416	neutral	N	0.50970739	None	None	N
T/C	0.5079	ambiguous	0.3978	ambiguous	-0.604	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
T/D	0.4712	ambiguous	0.335	benign	-0.024	Destabilizing	0.952	D	0.506	neutral	None	None	None	None	N
T/E	0.3049	likely_benign	0.2256	benign	0.005	Stabilizing	0.976	D	0.503	neutral	None	None	None	None	N
T/F	0.3603	ambiguous	0.2416	benign	-1.021	Destabilizing	0.976	D	0.635	neutral	None	None	None	None	N
T/G	0.3789	ambiguous	0.2775	benign	-1.234	Destabilizing	0.851	D	0.523	neutral	None	None	None	None	N
T/H	0.3203	likely_benign	0.2393	benign	-1.397	Destabilizing	0.997	D	0.637	neutral	None	None	None	None	N
T/I	0.1507	likely_benign	0.1028	benign	-0.306	Destabilizing	0.026	N	0.229	neutral	N	0.429323809	None	None	N
T/K	0.1967	likely_benign	0.1641	benign	-0.663	Destabilizing	0.968	D	0.521	neutral	N	0.468474056	None	None	N
T/L	0.1189	likely_benign	0.0866	benign	-0.306	Destabilizing	0.702	D	0.489	neutral	None	None	None	None	N
T/M	0.1209	likely_benign	0.0872	benign	-0.137	Destabilizing	0.993	D	0.584	neutral	None	None	None	None	N
T/N	0.1589	likely_benign	0.1121	benign	-0.703	Destabilizing	0.076	N	0.224	neutral	None	None	None	None	N
T/P	0.2609	likely_benign	0.1882	benign	-0.491	Destabilizing	0.995	D	0.581	neutral	N	0.475447389	None	None	N
T/Q	0.2278	likely_benign	0.1833	benign	-0.774	Destabilizing	0.988	D	0.573	neutral	None	None	None	None	N
T/R	0.1906	likely_benign	0.1494	benign	-0.486	Destabilizing	0.968	D	0.579	neutral	N	0.505010859	None	None	N
T/S	0.1556	likely_benign	0.1188	benign	-1.038	Destabilizing	0.811	D	0.422	neutral	N	0.484118299	None	None	N
T/V	0.1282	likely_benign	0.0962	benign	-0.491	Destabilizing	0.702	D	0.459	neutral	None	None	None	None	N
T/W	0.7238	likely_pathogenic	0.5943	pathogenic	-0.953	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
T/Y	0.4236	ambiguous	0.3148	benign	-0.707	Destabilizing	0.996	D	0.639	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.