TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5053	15382;15383;15384	chr2:178734767;178734766;178734765	chr2:179599494;179599493;179599492
N2AB	4736	14431;14432;14433	chr2:178734767;178734766;178734765	chr2:179599494;179599493;179599492
N2A	3809	11650;11651;11652	chr2:178734767;178734766;178734765	chr2:179599494;179599493;179599492
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: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-33
• Domain position: 73
• Structural Position: 155
• Q(SASA): 0.1933
• 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/L	None	None	0.811	N	0.632	0.252	0.529611391303	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
S/P	None	None	0.984	N	0.617	0.302	0.258779203287	gnomAD-4.0.0	1.59179E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8592E-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	0.1021	likely_benign	0.0995	benign	-0.967	Destabilizing	0.64	D	0.481	neutral	N	0.449939669	None	None	N
S/C	0.1352	likely_benign	0.1291	benign	-0.538	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
S/D	0.7495	likely_pathogenic	0.7011	pathogenic	-0.689	Destabilizing	0.919	D	0.567	neutral	None	None	None	None	N
S/E	0.775	likely_pathogenic	0.738	pathogenic	-0.533	Destabilizing	0.919	D	0.569	neutral	None	None	None	None	N
S/F	0.1813	likely_benign	0.1715	benign	-0.999	Destabilizing	0.988	D	0.69	prob.neutral	None	None	None	None	N
S/G	0.1723	likely_benign	0.1644	benign	-1.325	Destabilizing	0.919	D	0.593	neutral	None	None	None	None	N
S/H	0.421	ambiguous	0.3781	ambiguous	-1.58	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
S/I	0.1464	likely_benign	0.1384	benign	-0.065	Destabilizing	0.976	D	0.629	neutral	None	None	None	None	N
S/K	0.8577	likely_pathogenic	0.7891	pathogenic	0.096	Stabilizing	0.919	D	0.568	neutral	None	None	None	None	N
S/L	0.1086	likely_benign	0.1014	benign	-0.065	Destabilizing	0.811	D	0.632	neutral	N	0.447708667	None	None	N
S/M	0.2156	likely_benign	0.208	benign	-0.033	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
S/N	0.242	likely_benign	0.2194	benign	-0.409	Destabilizing	0.919	D	0.581	neutral	None	None	None	None	N
S/P	0.9803	likely_pathogenic	0.977	pathogenic	-0.333	Destabilizing	0.984	D	0.617	neutral	N	0.436207575	None	None	N
S/Q	0.6226	likely_pathogenic	0.5862	pathogenic	-0.306	Destabilizing	0.988	D	0.565	neutral	None	None	None	None	N
S/R	0.734	likely_pathogenic	0.6327	pathogenic	-0.198	Destabilizing	0.988	D	0.617	neutral	None	None	None	None	N
S/T	0.0749	likely_benign	0.0711	benign	-0.278	Destabilizing	0.016	N	0.337	neutral	N	0.3328232	None	None	N
S/V	0.1656	likely_benign	0.1524	benign	-0.333	Destabilizing	0.851	D	0.623	neutral	None	None	None	None	N
S/W	0.4467	ambiguous	0.4126	ambiguous	-1.052	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
S/Y	0.2119	likely_benign	0.1888	benign	-0.66	Destabilizing	0.996	D	0.696	prob.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.