TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5750	17473;17474;17475	chr2:178731518;178731517;178731516	chr2:179596245;179596244;179596243
N2AB	5433	16522;16523;16524	chr2:178731518;178731517;178731516	chr2:179596245;179596244;179596243
N2A	4506	13741;13742;13743	chr2:178731518;178731517;178731516	chr2:179596245;179596244;179596243
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-41
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.6301
• 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
Q/P	None	None	0.998	D	0.589	0.51	0.48512917806	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	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
Q/A	0.3593	ambiguous	0.3587	ambiguous	-0.78	Destabilizing	0.927	D	0.463	neutral	None	None	None	None	N
Q/C	0.7704	likely_pathogenic	0.749	pathogenic	-0.056	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
Q/D	0.572	likely_pathogenic	0.5521	ambiguous	-0.082	Destabilizing	0.939	D	0.416	neutral	None	None	None	None	N
Q/E	0.0951	likely_benign	0.0931	benign	0.032	Stabilizing	0.906	D	0.459	neutral	N	0.483878731	None	None	N
Q/F	0.749	likely_pathogenic	0.7488	pathogenic	-0.384	Destabilizing	0.991	D	0.622	neutral	None	None	None	None	N
Q/G	0.4762	ambiguous	0.4719	ambiguous	-1.142	Destabilizing	0.969	D	0.538	neutral	None	None	None	None	N
Q/H	0.2603	likely_benign	0.2619	benign	-0.743	Destabilizing	0.994	D	0.515	neutral	N	0.517263372	None	None	N
Q/I	0.4365	ambiguous	0.4264	ambiguous	0.149	Stabilizing	0.939	D	0.564	neutral	None	None	None	None	N
Q/K	0.1289	likely_benign	0.1218	benign	-0.176	Destabilizing	0.959	D	0.458	neutral	N	0.495301115	None	None	N
Q/L	0.1893	likely_benign	0.1918	benign	0.149	Stabilizing	0.068	N	0.404	neutral	N	0.516916656	None	None	N
Q/M	0.4775	ambiguous	0.4715	ambiguous	0.496	Stabilizing	0.736	D	0.355	neutral	None	None	None	None	N
Q/N	0.4638	ambiguous	0.4537	ambiguous	-0.729	Destabilizing	0.293	N	0.355	neutral	None	None	None	None	N
Q/P	0.6132	likely_pathogenic	0.6128	pathogenic	-0.13	Destabilizing	0.998	D	0.589	neutral	D	0.535945134	None	None	N
Q/R	0.1202	likely_benign	0.1167	benign	-0.112	Destabilizing	0.979	D	0.471	neutral	N	0.513972351	None	None	N
Q/S	0.3583	ambiguous	0.3345	benign	-0.943	Destabilizing	0.969	D	0.437	neutral	None	None	None	None	N
Q/T	0.2591	likely_benign	0.2386	benign	-0.62	Destabilizing	0.969	D	0.469	neutral	None	None	None	None	N
Q/V	0.2937	likely_benign	0.2885	benign	-0.13	Destabilizing	0.939	D	0.525	neutral	None	None	None	None	N
Q/W	0.6124	likely_pathogenic	0.6301	pathogenic	-0.178	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
Q/Y	0.5446	ambiguous	0.549	ambiguous	0.016	Stabilizing	0.999	D	0.589	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.