TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5968	18127;18128;18129	chr2:178730631;178730630;178730629	chr2:179595358;179595357;179595356
N2AB	5651	17176;17177;17178	chr2:178730631;178730630;178730629	chr2:179595358;179595357;179595356
N2A	4724	14395;14396;14397	chr2:178730631;178730630;178730629	chr2:179595358;179595357;179595356
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-43
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.323
• 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/C	None	None	0.999	N	0.395	0.465	0.593142052824	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31868E-05	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	0.135	likely_benign	0.1331	benign	-0.648	Destabilizing	0.675	D	0.235	neutral	N	0.497637462	None	None	N
S/C	0.2618	likely_benign	0.239	benign	-0.187	Destabilizing	0.999	D	0.395	neutral	N	0.508409075	None	None	N
S/D	0.7413	likely_pathogenic	0.7423	pathogenic	-0.097	Destabilizing	0.969	D	0.299	neutral	None	None	None	None	N
S/E	0.8219	likely_pathogenic	0.8221	pathogenic	-0.025	Destabilizing	0.969	D	0.25	neutral	None	None	None	None	N
S/F	0.3508	ambiguous	0.3537	ambiguous	-0.717	Destabilizing	0.976	D	0.477	neutral	N	0.491532588	None	None	N
S/G	0.2479	likely_benign	0.2345	benign	-0.946	Destabilizing	0.969	D	0.261	neutral	None	None	None	None	N
S/H	0.4938	ambiguous	0.485	ambiguous	-1.181	Destabilizing	0.999	D	0.396	neutral	None	None	None	None	N
S/I	0.2944	likely_benign	0.297	benign	0.063	Stabilizing	0.17	N	0.302	neutral	None	None	None	None	N
S/K	0.8863	likely_pathogenic	0.8936	pathogenic	-0.263	Destabilizing	0.969	D	0.238	neutral	None	None	None	None	N
S/L	0.16	likely_benign	0.1601	benign	0.063	Stabilizing	0.02	N	0.217	neutral	None	None	None	None	N
S/M	0.3415	ambiguous	0.3418	ambiguous	0.07	Stabilizing	0.982	D	0.418	neutral	None	None	None	None	N
S/N	0.3685	ambiguous	0.3788	ambiguous	-0.41	Destabilizing	0.969	D	0.331	neutral	None	None	None	None	N
S/P	0.9521	likely_pathogenic	0.9506	pathogenic	-0.14	Destabilizing	0.996	D	0.401	neutral	N	0.512675036	None	None	N
S/Q	0.7118	likely_pathogenic	0.7134	pathogenic	-0.368	Destabilizing	0.997	D	0.366	neutral	None	None	None	None	N
S/R	0.7858	likely_pathogenic	0.7892	pathogenic	-0.305	Destabilizing	0.991	D	0.401	neutral	None	None	None	None	N
S/T	0.112	likely_benign	0.1145	benign	-0.367	Destabilizing	0.061	N	0.087	neutral	N	0.445245772	None	None	N
S/V	0.2981	likely_benign	0.3043	benign	-0.14	Destabilizing	0.759	D	0.345	neutral	None	None	None	None	N
S/W	0.5396	ambiguous	0.5209	ambiguous	-0.826	Destabilizing	0.999	D	0.528	neutral	None	None	None	None	N
S/Y	0.3057	likely_benign	0.307	benign	-0.474	Destabilizing	0.996	D	0.498	neutral	N	0.493013845	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.