TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9270	28033;28034;28035	chr2:178712022;178712021;178712020	chr2:179576749;179576748;179576747
N2AB	8953	27082;27083;27084	chr2:178712022;178712021;178712020	chr2:179576749;179576748;179576747
N2A	8026	24301;24302;24303	chr2:178712022;178712021;178712020	chr2:179576749;179576748;179576747
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-78
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.4828
• Predicted PPI site: I

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	rs763189626	0.218	None	N	0.108	0.102	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	3.27E-05	None	0	1.77E-05	0
N/S	rs763189626	0.218	None	N	0.108	0.102	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs763189626	0.218	None	N	0.108	0.102	None	gnomAD-4.0.0	4.08994E-05	None	None	None	None	I	None	1.33447E-05	0	None	0	0	None	0	0	5.0857E-05	3.29482E-05	3.20215E-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	0.1269	likely_benign	0.1768	benign	-0.189	Destabilizing	None	N	0.126	neutral	None	None	None	None	I
N/C	0.2188	likely_benign	0.2998	benign	0.333	Stabilizing	0.676	D	0.268	neutral	None	None	None	None	I
N/D	0.0999	likely_benign	0.164	benign	0.167	Stabilizing	None	N	0.139	neutral	N	0.418284804	None	None	I
N/E	0.2312	likely_benign	0.3346	benign	0.111	Stabilizing	0.001	N	0.15	neutral	None	None	None	None	I
N/F	0.3117	likely_benign	0.3712	ambiguous	-0.724	Destabilizing	None	N	0.179	neutral	None	None	None	None	I
N/G	0.1518	likely_benign	0.1838	benign	-0.31	Destabilizing	0.016	N	0.166	neutral	None	None	None	None	I
N/H	0.0757	likely_benign	0.1032	benign	-0.357	Destabilizing	None	N	0.141	neutral	N	0.488243534	None	None	I
N/I	0.1484	likely_benign	0.1971	benign	0.033	Stabilizing	0.055	N	0.342	neutral	N	0.453730331	None	None	I
N/K	0.162	likely_benign	0.2454	benign	0.191	Stabilizing	0.012	N	0.101	neutral	N	0.437102638	None	None	I
N/L	0.1524	likely_benign	0.1694	benign	0.033	Stabilizing	0.016	N	0.274	neutral	None	None	None	None	I
N/M	0.216	likely_benign	0.2515	benign	0.284	Stabilizing	0.628	D	0.27	neutral	None	None	None	None	I
N/P	0.4478	ambiguous	0.5572	ambiguous	-0.017	Destabilizing	0.072	N	0.325	neutral	None	None	None	None	I
N/Q	0.1929	likely_benign	0.2552	benign	-0.216	Destabilizing	0.072	N	0.213	neutral	None	None	None	None	I
N/R	0.1743	likely_benign	0.2475	benign	0.253	Stabilizing	0.072	N	0.148	neutral	None	None	None	None	I
N/S	0.0616	likely_benign	0.0745	benign	0.011	Stabilizing	None	N	0.108	neutral	N	0.370568215	None	None	I
N/T	0.084	likely_benign	0.1056	benign	0.081	Stabilizing	0.012	N	0.115	neutral	N	0.432966255	None	None	I
N/V	0.1659	likely_benign	0.2278	benign	-0.017	Destabilizing	0.072	N	0.291	neutral	None	None	None	None	I
N/W	0.5267	ambiguous	0.6284	pathogenic	-0.799	Destabilizing	0.864	D	0.271	neutral	None	None	None	None	I
N/Y	0.1241	likely_benign	0.1491	benign	-0.492	Destabilizing	0.029	N	0.363	neutral	N	0.499633964	None	None	I

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.