TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5400	16423;16424;16425	chr2:178732978;178732977;178732976	chr2:179597705;179597704;179597703
N2AB	5083	15472;15473;15474	chr2:178732978;178732977;178732976	chr2:179597705;179597704;179597703
N2A	4156	12691;12692;12693	chr2:178732978;178732977;178732976	chr2:179597705;179597704;179597703
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-37
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2409
• 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/F	None	None	0.317	N	0.376	0.233	0.382592752248	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
S/P	None	None	0.484	N	0.347	0.123	0.28492961333	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85855E-06	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	0.1216	likely_benign	0.1259	benign	-0.407	Destabilizing	0.012	N	0.277	neutral	N	0.489401115	None	None	N
S/C	0.179	likely_benign	0.1752	benign	-0.344	Destabilizing	0.915	D	0.29	neutral	N	0.469422412	None	None	N
S/D	0.2928	likely_benign	0.2726	benign	0.312	Stabilizing	0.149	N	0.314	neutral	None	None	None	None	N
S/E	0.6002	likely_pathogenic	0.5834	pathogenic	0.253	Stabilizing	0.149	N	0.311	neutral	None	None	None	None	N
S/F	0.4092	ambiguous	0.4197	ambiguous	-0.934	Destabilizing	0.317	N	0.376	neutral	N	0.489906523	None	None	N
S/G	0.064	likely_benign	0.0616	benign	-0.555	Destabilizing	None	N	0.119	neutral	None	None	None	None	N
S/H	0.4681	ambiguous	0.4417	ambiguous	-0.931	Destabilizing	0.935	D	0.289	neutral	None	None	None	None	N
S/I	0.3901	ambiguous	0.3863	ambiguous	-0.145	Destabilizing	0.001	N	0.269	neutral	None	None	None	None	N
S/K	0.7212	likely_pathogenic	0.6947	pathogenic	-0.416	Destabilizing	0.149	N	0.323	neutral	None	None	None	None	N
S/L	0.1756	likely_benign	0.1818	benign	-0.145	Destabilizing	0.035	N	0.341	neutral	None	None	None	None	N
S/M	0.3298	likely_benign	0.3362	benign	-0.122	Destabilizing	0.38	N	0.291	neutral	None	None	None	None	N
S/N	0.1262	likely_benign	0.1141	benign	-0.255	Destabilizing	0.149	N	0.356	neutral	None	None	None	None	N
S/P	0.6094	likely_pathogenic	0.5889	pathogenic	-0.202	Destabilizing	0.484	N	0.347	neutral	N	0.461002167	None	None	N
S/Q	0.6465	likely_pathogenic	0.6182	pathogenic	-0.393	Destabilizing	0.555	D	0.335	neutral	None	None	None	None	N
S/R	0.6441	likely_pathogenic	0.611	pathogenic	-0.252	Destabilizing	0.38	N	0.334	neutral	None	None	None	None	N
S/T	0.0897	likely_benign	0.0919	benign	-0.321	Destabilizing	None	N	0.169	neutral	N	0.494537576	None	None	N
S/V	0.3452	ambiguous	0.3491	ambiguous	-0.202	Destabilizing	0.035	N	0.341	neutral	None	None	None	None	N
S/W	0.5541	ambiguous	0.5353	ambiguous	-0.979	Destabilizing	0.935	D	0.424	neutral	None	None	None	None	N
S/Y	0.3876	ambiguous	0.3764	ambiguous	-0.671	Destabilizing	0.484	N	0.361	neutral	N	0.471802268	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.