TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16854	50785;50786;50787	chr2:178611669;178611668;178611667	chr2:179476396;179476395;179476394
N2AB	15213	45862;45863;45864	chr2:178611669;178611668;178611667	chr2:179476396;179476395;179476394
N2A	14286	43081;43082;43083	chr2:178611669;178611668;178611667	chr2:179476396;179476395;179476394
N2B	7789	23590;23591;23592	chr2:178611669;178611668;178611667	chr2:179476396;179476395;179476394
Novex-1	7914	23965;23966;23967	chr2:178611669;178611668;178611667	chr2:179476396;179476395;179476394
Novex-2	7981	24166;24167;24168	chr2:178611669;178611668;178611667	chr2:179476396;179476395;179476394
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: Fn3-11
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2015
• 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	1.0	D	0.859	0.457	0.661710244528	gnomAD-4.0.0	3.18705E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72371E-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	0.193	likely_benign	0.2389	benign	-0.667	Destabilizing	0.997	D	0.707	prob.neutral	D	0.613066097	None	None	N
S/C	0.3689	ambiguous	0.4112	ambiguous	-0.622	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
S/D	0.8615	likely_pathogenic	0.9111	pathogenic	-1.068	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
S/E	0.9051	likely_pathogenic	0.9481	pathogenic	-1.002	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
S/F	0.6327	likely_pathogenic	0.7328	pathogenic	-0.569	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
S/G	0.1624	likely_benign	0.1736	benign	-0.987	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
S/H	0.8404	likely_pathogenic	0.8916	pathogenic	-1.464	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
S/I	0.6785	likely_pathogenic	0.8076	pathogenic	0.096	Stabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
S/K	0.9731	likely_pathogenic	0.9879	pathogenic	-0.875	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
S/L	0.2683	likely_benign	0.3555	ambiguous	0.096	Stabilizing	1.0	D	0.859	deleterious	D	0.652414251	None	None	N
S/M	0.5449	ambiguous	0.6358	pathogenic	0.269	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
S/N	0.5807	likely_pathogenic	0.68	pathogenic	-1.092	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
S/P	0.9432	likely_pathogenic	0.9614	pathogenic	-0.123	Destabilizing	1.0	D	0.859	deleterious	D	0.647328253	None	None	N
S/Q	0.8887	likely_pathogenic	0.9357	pathogenic	-1.125	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
S/R	0.9633	likely_pathogenic	0.9825	pathogenic	-0.891	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
S/T	0.1969	likely_benign	0.2685	benign	-0.924	Destabilizing	0.999	D	0.754	deleterious	D	0.532521139	None	None	N
S/V	0.6274	likely_pathogenic	0.7574	pathogenic	-0.123	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
S/W	0.8475	likely_pathogenic	0.8965	pathogenic	-0.674	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/Y	0.664	likely_pathogenic	0.7609	pathogenic	-0.36	Destabilizing	1.0	D	0.892	deleterious	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.