TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22301	67126;67127;67128	chr2:178580478;178580477;178580476	chr2:179445205;179445204;179445203
N2AB	20660	62203;62204;62205	chr2:178580478;178580477;178580476	chr2:179445205;179445204;179445203
N2A	19733	59422;59423;59424	chr2:178580478;178580477;178580476	chr2:179445205;179445204;179445203
N2B	13236	39931;39932;39933	chr2:178580478;178580477;178580476	chr2:179445205;179445204;179445203
Novex-1	13361	40306;40307;40308	chr2:178580478;178580477;178580476	chr2:179445205;179445204;179445203
Novex-2	13428	40507;40508;40509	chr2:178580478;178580477;178580476	chr2:179445205;179445204;179445203
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-126
• Domain position: 37
• Structural Position: 56
• Q(SASA): 0.4687
• 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
N/S	rs772823241	0.046	0.822	N	0.423	0.268	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	1.78E-05	0
N/S	rs772823241	0.046	0.822	N	0.423	0.268	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
N/S	rs772823241	0.046	0.822	N	0.423	0.268	None	gnomAD-4.0.0	3.03787E-05	None	None	None	None	N	None	1.33554E-05	0	None	0	2.23724E-05	None	0	0	3.90016E-05	0	1.60251E-05

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
N/A	0.257	likely_benign	0.2293	benign	-0.127	Destabilizing	0.86	D	0.485	neutral	None	None	None	None	N
N/C	0.2849	likely_benign	0.2635	benign	0.292	Stabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
N/D	0.1625	likely_benign	0.1703	benign	0.216	Stabilizing	0.014	N	0.297	neutral	N	0.428929525	None	None	N
N/E	0.4559	ambiguous	0.4544	ambiguous	0.17	Stabilizing	0.754	D	0.402	neutral	None	None	None	None	N
N/F	0.6224	likely_pathogenic	0.6014	pathogenic	-0.633	Destabilizing	0.978	D	0.683	prob.neutral	None	None	None	None	N
N/G	0.4128	ambiguous	0.3811	ambiguous	-0.263	Destabilizing	0.86	D	0.401	neutral	None	None	None	None	N
N/H	0.1453	likely_benign	0.1344	benign	-0.294	Destabilizing	0.99	D	0.536	neutral	D	0.534000907	None	None	N
N/I	0.2348	likely_benign	0.2105	benign	0.133	Stabilizing	0.89	D	0.589	neutral	N	0.484516236	None	None	N
N/K	0.4103	ambiguous	0.3908	ambiguous	0.158	Stabilizing	0.822	D	0.439	neutral	N	0.499154827	None	None	N
N/L	0.2715	likely_benign	0.2532	benign	0.133	Stabilizing	0.754	D	0.552	neutral	None	None	None	None	N
N/M	0.3873	ambiguous	0.3523	ambiguous	0.245	Stabilizing	0.994	D	0.649	neutral	None	None	None	None	N
N/P	0.3192	likely_benign	0.2992	benign	0.072	Stabilizing	0.978	D	0.628	neutral	None	None	None	None	N
N/Q	0.367	ambiguous	0.3433	ambiguous	-0.209	Destabilizing	0.978	D	0.524	neutral	None	None	None	None	N
N/R	0.4367	ambiguous	0.4227	ambiguous	0.193	Stabilizing	0.978	D	0.526	neutral	None	None	None	None	N
N/S	0.1	likely_benign	0.0943	benign	-0.009	Destabilizing	0.822	D	0.423	neutral	N	0.493018289	None	None	N
N/T	0.1591	likely_benign	0.1432	benign	0.075	Stabilizing	0.822	D	0.438	neutral	N	0.489940698	None	None	N
N/V	0.236	likely_benign	0.1994	benign	0.072	Stabilizing	0.16	N	0.411	neutral	None	None	None	None	N
N/W	0.842	likely_pathogenic	0.8363	pathogenic	-0.723	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
N/Y	0.2347	likely_benign	0.2419	benign	-0.408	Destabilizing	0.99	D	0.641	neutral	D	0.534347623	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.