TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6846	20761;20762;20763	chr2:178725786;178725785;178725784	chr2:179590513;179590512;179590511
N2AB	6529	19810;19811;19812	chr2:178725786;178725785;178725784	chr2:179590513;179590512;179590511
N2A	5602	17029;17030;17031	chr2:178725786;178725785;178725784	chr2:179590513;179590512;179590511
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-52
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0957
• 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
C/G	None	None	0.001	N	0.469	0.334	0.509228182784	gnomAD-4.0.0	1.61786E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.90973E-06	0	0
C/S	None	None	0.27	N	0.553	0.234	0.586357277508	gnomAD-4.0.0	2.0691E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81004E-06	0	1.67034E-05
C/Y	rs947572697	None	0.473	N	0.783	0.273	0.634282618606	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
C/Y	rs947572697	None	0.473	N	0.783	0.273	0.634282618606	gnomAD-4.0.0	1.87261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.55764E-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
C/A	0.3569	ambiguous	0.2982	benign	-1.565	Destabilizing	0.013	N	0.133	neutral	None	None	None	None	N
C/D	0.9161	likely_pathogenic	0.8985	pathogenic	-1.689	Destabilizing	0.704	D	0.705	prob.neutral	None	None	None	None	N
C/E	0.9592	likely_pathogenic	0.9516	pathogenic	-1.437	Destabilizing	0.704	D	0.68	prob.neutral	None	None	None	None	N
C/F	0.2826	likely_benign	0.2833	benign	-0.904	Destabilizing	0.006	N	0.499	neutral	N	0.504774078	None	None	N
C/G	0.1532	likely_benign	0.1406	benign	-1.915	Destabilizing	0.001	N	0.469	neutral	N	0.437666438	None	None	N
C/H	0.8053	likely_pathogenic	0.7964	pathogenic	-2.122	Highly Destabilizing	0.981	D	0.757	deleterious	None	None	None	None	N
C/I	0.6019	likely_pathogenic	0.5449	ambiguous	-0.604	Destabilizing	0.704	D	0.703	prob.neutral	None	None	None	None	N
C/K	0.9603	likely_pathogenic	0.9579	pathogenic	-1.162	Destabilizing	0.013	N	0.525	neutral	None	None	None	None	N
C/L	0.5581	ambiguous	0.5464	ambiguous	-0.604	Destabilizing	0.329	N	0.566	neutral	None	None	None	None	N
C/M	0.7038	likely_pathogenic	0.6813	pathogenic	-0.031	Destabilizing	0.981	D	0.759	deleterious	None	None	None	None	N
C/N	0.7671	likely_pathogenic	0.7315	pathogenic	-1.828	Destabilizing	0.704	D	0.734	prob.delet.	None	None	None	None	N
C/P	0.984	likely_pathogenic	0.9854	pathogenic	-0.904	Destabilizing	0.828	D	0.787	deleterious	None	None	None	None	N
C/Q	0.8719	likely_pathogenic	0.8645	pathogenic	-1.289	Destabilizing	0.893	D	0.808	deleterious	None	None	None	None	N
C/R	0.8093	likely_pathogenic	0.8069	pathogenic	-1.668	Destabilizing	0.473	N	0.733	prob.delet.	D	0.532211395	None	None	N
C/S	0.2993	likely_benign	0.2495	benign	-2.087	Highly Destabilizing	0.27	N	0.553	neutral	N	0.453673254	None	None	N
C/T	0.4403	ambiguous	0.3555	ambiguous	-1.664	Destabilizing	0.013	N	0.405	neutral	None	None	None	None	N
C/V	0.4766	ambiguous	0.4191	ambiguous	-0.904	Destabilizing	0.495	N	0.585	neutral	None	None	None	None	N
C/W	0.7609	likely_pathogenic	0.7545	pathogenic	-1.387	Destabilizing	0.993	D	0.733	prob.delet.	D	0.524573347	None	None	N
C/Y	0.5284	ambiguous	0.52	ambiguous	-1.164	Destabilizing	0.473	N	0.783	deleterious	N	0.487055109	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.