TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29221	87886;87887;87888	chr2:178557693;178557692;178557691	chr2:179422420;179422419;179422418
N2AB	27580	82963;82964;82965	chr2:178557693;178557692;178557691	chr2:179422420;179422419;179422418
N2A	26653	80182;80183;80184	chr2:178557693;178557692;178557691	chr2:179422420;179422419;179422418
N2B	20156	60691;60692;60693	chr2:178557693;178557692;178557691	chr2:179422420;179422419;179422418
Novex-1	20281	61066;61067;61068	chr2:178557693;178557692;178557691	chr2:179422420;179422419;179422418
Novex-2	20348	61267;61268;61269	chr2:178557693;178557692;178557691	chr2:179422420;179422419;179422418
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-100
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.0686
• 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/G	None	None	0.999	N	0.617	0.445	0.178374595973	gnomAD-4.0.0	1.59102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85778E-06	0	0
S/N	None	None	0.999	D	0.639	0.507	0.364730456448	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5442	ambiguous	0.5521	ambiguous	-0.834	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
S/C	0.8012	likely_pathogenic	0.8243	pathogenic	-0.842	Destabilizing	1.0	D	0.801	deleterious	D	0.545942306	None	None	N
S/D	0.9943	likely_pathogenic	0.9956	pathogenic	-1.348	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
S/E	0.9982	likely_pathogenic	0.9985	pathogenic	-1.251	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
S/F	0.9972	likely_pathogenic	0.9975	pathogenic	-0.612	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
S/G	0.1672	likely_benign	0.2017	benign	-1.161	Destabilizing	0.999	D	0.617	neutral	N	0.46566025	None	None	N
S/H	0.9939	likely_pathogenic	0.9942	pathogenic	-1.485	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
S/I	0.9973	likely_pathogenic	0.9979	pathogenic	-0.039	Destabilizing	1.0	D	0.771	deleterious	D	0.534332511	None	None	N
S/K	0.9996	likely_pathogenic	0.9996	pathogenic	-0.898	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
S/L	0.9789	likely_pathogenic	0.9816	pathogenic	-0.039	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
S/M	0.9896	likely_pathogenic	0.9908	pathogenic	-0.016	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
S/N	0.9789	likely_pathogenic	0.9819	pathogenic	-1.201	Destabilizing	0.999	D	0.639	neutral	D	0.544674858	None	None	N
S/P	0.9958	likely_pathogenic	0.9962	pathogenic	-0.27	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/Q	0.9967	likely_pathogenic	0.997	pathogenic	-1.201	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
S/R	0.9986	likely_pathogenic	0.9987	pathogenic	-0.904	Destabilizing	1.0	D	0.769	deleterious	D	0.545181837	None	None	N
S/T	0.8261	likely_pathogenic	0.8458	pathogenic	-1.01	Destabilizing	0.999	D	0.59	neutral	D	0.532558084	None	None	N
S/V	0.9952	likely_pathogenic	0.9959	pathogenic	-0.27	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
S/W	0.9963	likely_pathogenic	0.9966	pathogenic	-0.728	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
S/Y	0.9947	likely_pathogenic	0.9953	pathogenic	-0.406	Destabilizing	1.0	D	0.813	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.