TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29109	87550;87551;87552	chr2:178558029;178558028;178558027	chr2:179422756;179422755;179422754
N2AB	27468	82627;82628;82629	chr2:178558029;178558028;178558027	chr2:179422756;179422755;179422754
N2A	26541	79846;79847;79848	chr2:178558029;178558028;178558027	chr2:179422756;179422755;179422754
N2B	20044	60355;60356;60357	chr2:178558029;178558028;178558027	chr2:179422756;179422755;179422754
Novex-1	20169	60730;60731;60732	chr2:178558029;178558028;178558027	chr2:179422756;179422755;179422754
Novex-2	20236	60931;60932;60933	chr2:178558029;178558028;178558027	chr2:179422756;179422755;179422754
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: Ig-145
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5581
• 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	rs753496654	0.008	None	N	0.197	0.165	0.159798565429	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.79E-05	None	0	0	None	0	None	0	0	0
T/I	rs753496654	0.008	None	N	0.197	0.165	0.159798565429	gnomAD-4.0.0	3.18221E-06	None	None	None	None	N	None	0	4.57247E-05	None	0	0	None	0	0	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	0.0476	likely_benign	0.0467	benign	-0.278	Destabilizing	None	N	0.091	neutral	N	0.338727942	None	None	N
T/C	0.3171	likely_benign	0.278	benign	-0.31	Destabilizing	0.356	N	0.295	neutral	None	None	None	None	N
T/D	0.3657	ambiguous	0.3458	ambiguous	0.061	Stabilizing	0.072	N	0.326	neutral	None	None	None	None	N
T/E	0.2738	likely_benign	0.2625	benign	-0.028	Destabilizing	0.072	N	0.275	neutral	None	None	None	None	N
T/F	0.2129	likely_benign	0.1939	benign	-0.838	Destabilizing	0.214	N	0.378	neutral	None	None	None	None	N
T/G	0.1519	likely_benign	0.1415	benign	-0.374	Destabilizing	0.016	N	0.302	neutral	None	None	None	None	N
T/H	0.2689	likely_benign	0.2359	benign	-0.592	Destabilizing	0.628	D	0.337	neutral	None	None	None	None	N
T/I	0.1092	likely_benign	0.106	benign	-0.147	Destabilizing	None	N	0.197	neutral	N	0.4086466	None	None	N
T/K	0.2149	likely_benign	0.1888	benign	-0.362	Destabilizing	0.055	N	0.269	neutral	N	0.362970239	None	None	N
T/L	0.0861	likely_benign	0.0798	benign	-0.147	Destabilizing	0.002	N	0.255	neutral	None	None	None	None	N
T/M	0.0797	likely_benign	0.0759	benign	-0.051	Destabilizing	0.214	N	0.288	neutral	None	None	None	None	N
T/N	0.1192	likely_benign	0.1179	benign	-0.139	Destabilizing	0.136	N	0.223	neutral	None	None	None	None	N
T/P	0.0795	likely_benign	0.0726	benign	-0.164	Destabilizing	0.055	N	0.309	neutral	N	0.377976977	None	None	N
T/Q	0.2223	likely_benign	0.1987	benign	-0.379	Destabilizing	0.356	N	0.321	neutral	None	None	None	None	N
T/R	0.198	likely_benign	0.171	benign	-0.051	Destabilizing	0.055	N	0.327	neutral	N	0.311194624	None	None	N
T/S	0.0918	likely_benign	0.089	benign	-0.327	Destabilizing	0.012	N	0.231	neutral	N	0.39006084	None	None	N
T/V	0.0863	likely_benign	0.0828	benign	-0.164	Destabilizing	0.002	N	0.178	neutral	None	None	None	None	N
T/W	0.5861	likely_pathogenic	0.5303	ambiguous	-0.872	Destabilizing	0.864	D	0.363	neutral	None	None	None	None	N
T/Y	0.264	likely_benign	0.2274	benign	-0.577	Destabilizing	0.356	N	0.356	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.