TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27068	81427;81428;81429	chr2:178564930;178564929;178564928	chr2:179429657;179429656;179429655
N2AB	25427	76504;76505;76506	chr2:178564930;178564929;178564928	chr2:179429657;179429656;179429655
N2A	24500	73723;73724;73725	chr2:178564930;178564929;178564928	chr2:179429657;179429656;179429655
N2B	18003	54232;54233;54234	chr2:178564930;178564929;178564928	chr2:179429657;179429656;179429655
Novex-1	18128	54607;54608;54609	chr2:178564930;178564929;178564928	chr2:179429657;179429656;179429655
Novex-2	18195	54808;54809;54810	chr2:178564930;178564929;178564928	chr2:179429657;179429656;179429655
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-84
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.8213
• 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
Y/H	None	None	0.015	N	0.334	0.217	0.24896430686	gnomAD-4.0.0	1.59509E-06	None	None	None	None	N	None	5.70972E-05	0	None	0	0	None	0	0	0	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
Y/A	0.9163	likely_pathogenic	0.9094	pathogenic	-0.488	Destabilizing	0.74	D	0.531	neutral	None	None	None	None	N
Y/C	0.6769	likely_pathogenic	0.6371	pathogenic	0.119	Stabilizing	0.994	D	0.865	deleterious	N	0.483744913	None	None	N
Y/D	0.7681	likely_pathogenic	0.798	pathogenic	0.867	Stabilizing	0.883	D	0.842	deleterious	N	0.474839881	None	None	N
Y/E	0.9651	likely_pathogenic	0.9604	pathogenic	0.843	Stabilizing	0.909	D	0.611	neutral	None	None	None	None	N
Y/F	0.2373	likely_benign	0.2115	benign	-0.235	Destabilizing	0.007	N	0.274	neutral	N	0.465044773	None	None	N
Y/G	0.8844	likely_pathogenic	0.8836	pathogenic	-0.659	Destabilizing	0.909	D	0.588	neutral	None	None	None	None	N
Y/H	0.4824	ambiguous	0.4304	ambiguous	0.313	Stabilizing	0.015	N	0.334	neutral	N	0.496831306	None	None	N
Y/I	0.9029	likely_pathogenic	0.9023	pathogenic	-0.072	Destabilizing	0.909	D	0.549	neutral	None	None	None	None	N
Y/K	0.9453	likely_pathogenic	0.9414	pathogenic	0.254	Stabilizing	0.909	D	0.808	deleterious	None	None	None	None	N
Y/L	0.6801	likely_pathogenic	0.6694	pathogenic	-0.072	Destabilizing	0.587	D	0.527	neutral	None	None	None	None	N
Y/M	0.8826	likely_pathogenic	0.8806	pathogenic	-0.055	Destabilizing	0.996	D	0.528	neutral	None	None	None	None	N
Y/N	0.5213	ambiguous	0.5171	ambiguous	0.023	Stabilizing	0.883	D	0.851	deleterious	N	0.493233641	None	None	N
Y/P	0.9096	likely_pathogenic	0.8973	pathogenic	-0.191	Destabilizing	0.984	D	0.846	deleterious	None	None	None	None	N
Y/Q	0.9424	likely_pathogenic	0.9311	pathogenic	0.088	Stabilizing	0.909	D	0.553	neutral	None	None	None	None	N
Y/R	0.9276	likely_pathogenic	0.9166	pathogenic	0.446	Stabilizing	0.909	D	0.854	deleterious	None	None	None	None	N
Y/S	0.6826	likely_pathogenic	0.6783	pathogenic	-0.353	Destabilizing	0.883	D	0.563	neutral	N	0.500967689	None	None	N
Y/T	0.9125	likely_pathogenic	0.9079	pathogenic	-0.285	Destabilizing	0.953	D	0.789	deleterious	None	None	None	None	N
Y/V	0.8612	likely_pathogenic	0.8589	pathogenic	-0.191	Destabilizing	0.74	D	0.547	neutral	None	None	None	None	N
Y/W	0.7363	likely_pathogenic	0.7365	pathogenic	-0.412	Destabilizing	0.996	D	0.569	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.