TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26910	80953;80954;80955	chr2:178565404;178565403;178565402	chr2:179430131;179430130;179430129
N2AB	25269	76030;76031;76032	chr2:178565404;178565403;178565402	chr2:179430131;179430130;179430129
N2A	24342	73249;73250;73251	chr2:178565404;178565403;178565402	chr2:179430131;179430130;179430129
N2B	17845	53758;53759;53760	chr2:178565404;178565403;178565402	chr2:179430131;179430130;179430129
Novex-1	17970	54133;54134;54135	chr2:178565404;178565403;178565402	chr2:179430131;179430130;179430129
Novex-2	18037	54334;54335;54336	chr2:178565404;178565403;178565402	chr2:179430131;179430130;179430129
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-139
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.5233
• 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/D	rs1456879074	0.126	0.003	N	0.213	0.148	0.136095386433	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
N/D	rs1456879074	0.126	0.003	N	0.213	0.148	0.136095386433	gnomAD-4.0.0	1.59173E-06	None	None	None	None	I	None	0	2.28676E-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
N/A	0.0692	likely_benign	0.0733	benign	-0.382	Destabilizing	None	N	0.21	neutral	None	None	None	None	I
N/C	0.1333	likely_benign	0.142	benign	0.31	Stabilizing	0.245	N	0.512	neutral	None	None	None	None	I
N/D	0.1102	likely_benign	0.104	benign	0.019	Stabilizing	0.003	N	0.213	neutral	N	0.433124623	None	None	I
N/E	0.1328	likely_benign	0.1336	benign	-0.011	Destabilizing	None	N	0.091	neutral	None	None	None	None	I
N/F	0.2613	likely_benign	0.2743	benign	-0.705	Destabilizing	0.085	N	0.584	neutral	None	None	None	None	I
N/G	0.1307	likely_benign	0.1296	benign	-0.567	Destabilizing	0.002	N	0.205	neutral	None	None	None	None	I
N/H	0.0685	likely_benign	0.0691	benign	-0.603	Destabilizing	0.196	N	0.378	neutral	N	0.471144294	None	None	I
N/I	0.0849	likely_benign	0.0863	benign	0.023	Stabilizing	0.007	N	0.483	neutral	N	0.455790839	None	None	I
N/K	0.08	likely_benign	0.0796	benign	0.031	Stabilizing	None	N	0.079	neutral	N	0.366072912	None	None	I
N/L	0.0931	likely_benign	0.0979	benign	0.023	Stabilizing	0.004	N	0.298	neutral	None	None	None	None	I
N/M	0.1362	likely_benign	0.1401	benign	0.371	Stabilizing	0.245	N	0.521	neutral	None	None	None	None	I
N/P	0.5372	ambiguous	0.5348	ambiguous	-0.085	Destabilizing	0.037	N	0.416	neutral	None	None	None	None	I
N/Q	0.104	likely_benign	0.1053	benign	-0.443	Destabilizing	0.009	N	0.236	neutral	None	None	None	None	I
N/R	0.0993	likely_benign	0.1052	benign	0.078	Stabilizing	0.004	N	0.215	neutral	None	None	None	None	I
N/S	0.0545	likely_benign	0.0554	benign	-0.201	Destabilizing	None	N	0.085	neutral	N	0.394219518	None	None	I
N/T	0.0535	likely_benign	0.0568	benign	-0.085	Destabilizing	None	N	0.079	neutral	N	0.341907973	None	None	I
N/V	0.0731	likely_benign	0.0754	benign	-0.085	Destabilizing	0.004	N	0.303	neutral	None	None	None	None	I
N/W	0.5408	ambiguous	0.5607	ambiguous	-0.668	Destabilizing	0.788	D	0.501	neutral	None	None	None	None	I
N/Y	0.1165	likely_benign	0.1196	benign	-0.413	Destabilizing	0.065	N	0.572	neutral	N	0.512164197	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.