TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7975	24148;24149;24150	chr2:178719569;178719568;178719567	chr2:179584296;179584295;179584294
N2AB	7658	23197;23198;23199	chr2:178719569;178719568;178719567	chr2:179584296;179584295;179584294
N2A	6731	20416;20417;20418	chr2:178719569;178719568;178719567	chr2:179584296;179584295;179584294
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-64
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.1537
• 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
S/C	rs2078029519	None	0.999	N	0.663	0.46	0.77112915265	gnomAD-4.0.0	2.06075E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80574E-06	0	1.66312E-05
S/F	None	None	0.996	N	0.688	0.421	0.823965795647	gnomAD-4.0.0	6.86917E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02869E-07	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
S/A	0.0785	likely_benign	0.0803	benign	-0.606	Destabilizing	0.826	D	0.475	neutral	N	0.493988123	None	None	N
S/C	0.1734	likely_benign	0.1935	benign	-0.373	Destabilizing	0.999	D	0.663	neutral	N	0.517411977	None	None	N
S/D	0.3425	ambiguous	0.3275	benign	-0.15	Destabilizing	0.884	D	0.616	neutral	None	None	None	None	N
S/E	0.4751	ambiguous	0.4513	ambiguous	-0.102	Destabilizing	0.863	D	0.577	neutral	None	None	None	None	N
S/F	0.1908	likely_benign	0.2066	benign	-0.587	Destabilizing	0.996	D	0.688	prob.neutral	N	0.489899973	None	None	N
S/G	0.1485	likely_benign	0.1427	benign	-0.914	Destabilizing	0.863	D	0.58	neutral	None	None	None	None	N
S/H	0.3709	ambiguous	0.3709	ambiguous	-1.372	Destabilizing	0.991	D	0.687	prob.neutral	None	None	None	None	N
S/I	0.2037	likely_benign	0.2205	benign	0.119	Stabilizing	0.982	D	0.711	prob.delet.	None	None	None	None	N
S/K	0.6734	likely_pathogenic	0.6699	pathogenic	-0.564	Destabilizing	0.17	N	0.265	neutral	None	None	None	None	N
S/L	0.0997	likely_benign	0.1099	benign	0.119	Stabilizing	0.939	D	0.658	neutral	None	None	None	None	N
S/M	0.2053	likely_benign	0.2212	benign	0.197	Stabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
S/N	0.1546	likely_benign	0.1527	benign	-0.63	Destabilizing	0.17	N	0.269	neutral	None	None	None	None	N
S/P	0.2095	likely_benign	0.1745	benign	-0.087	Destabilizing	0.996	D	0.725	prob.delet.	D	0.523652948	None	None	N
S/Q	0.5128	ambiguous	0.5175	ambiguous	-0.635	Destabilizing	0.939	D	0.666	neutral	None	None	None	None	N
S/R	0.5821	likely_pathogenic	0.5718	pathogenic	-0.642	Destabilizing	0.046	N	0.491	neutral	None	None	None	None	N
S/T	0.091	likely_benign	0.0943	benign	-0.574	Destabilizing	0.134	N	0.251	neutral	N	0.431009825	None	None	N
S/V	0.1961	likely_benign	0.2105	benign	-0.087	Destabilizing	0.939	D	0.673	neutral	None	None	None	None	N
S/W	0.3158	likely_benign	0.3222	benign	-0.644	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
S/Y	0.1787	likely_benign	0.1861	benign	-0.333	Destabilizing	0.996	D	0.687	prob.neutral	N	0.49550906	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.