TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5909	17950;17951;17952	chr2:178730940;178730939;178730938	chr2:179595667;179595666;179595665
N2AB	5592	16999;17000;17001	chr2:178730940;178730939;178730938	chr2:179595667;179595666;179595665
N2A	4665	14218;14219;14220	chr2:178730940;178730939;178730938	chr2:179595667;179595666;179595665
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-42
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.5466
• 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
R/I	rs2080369871	None	0.003	N	0.345	0.129	0.598143334274	gnomAD-4.0.0	1.61471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.90097E-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
R/A	0.0946	likely_benign	0.1033	benign	-0.813	Destabilizing	None	N	0.181	neutral	None	None	None	None	N
R/C	0.0908	likely_benign	0.1026	benign	-0.775	Destabilizing	0.132	N	0.481	neutral	None	None	None	None	N
R/D	0.2019	likely_benign	0.242	benign	-0.131	Destabilizing	0.002	N	0.298	neutral	None	None	None	None	N
R/E	0.1616	likely_benign	0.1757	benign	-0.059	Destabilizing	0.002	N	0.206	neutral	None	None	None	None	N
R/F	0.2115	likely_benign	0.2325	benign	-0.986	Destabilizing	0.041	N	0.541	neutral	None	None	None	None	N
R/G	0.083	likely_benign	0.0957	benign	-1.046	Destabilizing	None	N	0.202	neutral	N	0.482832401	None	None	N
R/H	0.0651	likely_benign	0.068	benign	-1.28	Destabilizing	0.132	N	0.453	neutral	None	None	None	None	N
R/I	0.104	likely_benign	0.1127	benign	-0.212	Destabilizing	0.003	N	0.345	neutral	N	0.484785595	None	None	N
R/K	0.0758	likely_benign	0.0775	benign	-0.776	Destabilizing	0.001	N	0.206	neutral	N	0.470488146	None	None	N
R/L	0.113	likely_benign	0.1171	benign	-0.212	Destabilizing	0.001	N	0.31	neutral	None	None	None	None	N
R/M	0.1107	likely_benign	0.1093	benign	-0.327	Destabilizing	0.132	N	0.513	neutral	None	None	None	None	N
R/N	0.1237	likely_benign	0.1483	benign	-0.176	Destabilizing	None	N	0.105	neutral	None	None	None	None	N
R/P	0.5284	ambiguous	0.6106	pathogenic	-0.393	Destabilizing	0.009	N	0.404	neutral	None	None	None	None	N
R/Q	0.0732	likely_benign	0.0716	benign	-0.498	Destabilizing	0.009	N	0.383	neutral	None	None	None	None	N
R/S	0.0823	likely_benign	0.0959	benign	-0.955	Destabilizing	None	N	0.167	neutral	N	0.427236014	None	None	N
R/T	0.0598	likely_benign	0.0626	benign	-0.734	Destabilizing	None	N	0.158	neutral	N	0.396779821	None	None	N
R/V	0.1307	likely_benign	0.139	benign	-0.393	Destabilizing	None	N	0.302	neutral	None	None	None	None	N
R/W	0.1202	likely_benign	0.1192	benign	-0.709	Destabilizing	0.316	N	0.475	neutral	None	None	None	None	N
R/Y	0.1498	likely_benign	0.1609	benign	-0.371	Destabilizing	0.041	N	0.514	neutral	None	None	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.