TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32418	97477;97478;97479	chr2:178542504;178542503;178542502	chr2:179407231;179407230;179407229
N2AB	30777	92554;92555;92556	chr2:178542504;178542503;178542502	chr2:179407231;179407230;179407229
N2A	29850	89773;89774;89775	chr2:178542504;178542503;178542502	chr2:179407231;179407230;179407229
N2B	23353	70282;70283;70284	chr2:178542504;178542503;178542502	chr2:179407231;179407230;179407229
Novex-1	23478	70657;70658;70659	chr2:178542504;178542503;178542502	chr2:179407231;179407230;179407229
Novex-2	23545	70858;70859;70860	chr2:178542504;178542503;178542502	chr2:179407231;179407230;179407229
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: Fn3-124
• Domain position: 20
• Structural Position: 21
• Q(SASA): 0.1772
• 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	rs771893617	-1.55	0.016	N	0.466	0.098	0.173771789658	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.30899E-04	None	0	0	0
T/S	rs771893617	-1.55	0.016	N	0.466	0.098	0.173771789658	gnomAD-4.0.0	1.43498E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.29029E-04	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	0.1185	likely_benign	0.0972	benign	-1.188	Destabilizing	0.201	N	0.523	neutral	N	0.485829416	None	None	N
T/C	0.3563	ambiguous	0.2828	benign	-1.258	Destabilizing	0.992	D	0.599	neutral	None	None	None	None	N
T/D	0.7511	likely_pathogenic	0.6952	pathogenic	-1.903	Destabilizing	0.85	D	0.621	neutral	None	None	None	None	N
T/E	0.5965	likely_pathogenic	0.5441	ambiguous	-1.749	Destabilizing	0.617	D	0.603	neutral	None	None	None	None	N
T/F	0.3854	ambiguous	0.3143	benign	-1.048	Destabilizing	0.85	D	0.615	neutral	None	None	None	None	N
T/G	0.3711	ambiguous	0.2911	benign	-1.53	Destabilizing	0.447	N	0.571	neutral	None	None	None	None	N
T/H	0.4174	ambiguous	0.3559	ambiguous	-1.684	Destabilizing	0.992	D	0.61	neutral	None	None	None	None	N
T/I	0.1897	likely_benign	0.1633	benign	-0.316	Destabilizing	0.004	N	0.417	neutral	D	0.524735557	None	None	N
T/K	0.4099	ambiguous	0.3811	ambiguous	-0.792	Destabilizing	0.617	D	0.601	neutral	None	None	None	None	N
T/L	0.1416	likely_benign	0.1138	benign	-0.316	Destabilizing	0.103	N	0.505	neutral	None	None	None	None	N
T/M	0.1078	likely_benign	0.0896	benign	-0.367	Destabilizing	0.25	N	0.473	neutral	None	None	None	None	N
T/N	0.2437	likely_benign	0.1956	benign	-1.399	Destabilizing	0.81	D	0.603	neutral	N	0.473739096	None	None	N
T/P	0.7926	likely_pathogenic	0.7913	pathogenic	-0.576	Destabilizing	0.896	D	0.619	neutral	N	0.519026186	None	None	N
T/Q	0.3725	ambiguous	0.3246	benign	-1.347	Destabilizing	0.92	D	0.61	neutral	None	None	None	None	N
T/R	0.3541	ambiguous	0.3111	benign	-0.794	Destabilizing	0.85	D	0.621	neutral	None	None	None	None	N
T/S	0.1536	likely_benign	0.1272	benign	-1.541	Destabilizing	0.016	N	0.466	neutral	N	0.500010471	None	None	N
T/V	0.1403	likely_benign	0.1204	benign	-0.576	Destabilizing	0.005	N	0.351	neutral	None	None	None	None	N
T/W	0.742	likely_pathogenic	0.6774	pathogenic	-1.172	Destabilizing	0.992	D	0.648	neutral	None	None	None	None	N
T/Y	0.4384	ambiguous	0.3856	ambiguous	-0.792	Destabilizing	0.92	D	0.626	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.