TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26462	79609;79610;79611	chr2:178566748;178566747;178566746	chr2:179431475;179431474;179431473
N2AB	24821	74686;74687;74688	chr2:178566748;178566747;178566746	chr2:179431475;179431474;179431473
N2A	23894	71905;71906;71907	chr2:178566748;178566747;178566746	chr2:179431475;179431474;179431473
N2B	17397	52414;52415;52416	chr2:178566748;178566747;178566746	chr2:179431475;179431474;179431473
Novex-1	17522	52789;52790;52791	chr2:178566748;178566747;178566746	chr2:179431475;179431474;179431473
Novex-2	17589	52990;52991;52992	chr2:178566748;178566747;178566746	chr2:179431475;179431474;179431473
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: Fn3-80
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1141
• 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/P	None	None	0.983	N	0.717	0.468	0.386721274199	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	0.0774	likely_benign	0.0769	benign	-1.363	Destabilizing	0.63	D	0.616	neutral	N	0.445058479	None	None	N
S/C	0.0699	likely_benign	0.0826	benign	-1.257	Destabilizing	0.999	D	0.72	prob.delet.	N	0.472445195	None	None	N
S/D	0.8934	likely_pathogenic	0.9061	pathogenic	-2.247	Highly Destabilizing	0.916	D	0.639	neutral	None	None	None	None	N
S/E	0.8579	likely_pathogenic	0.8673	pathogenic	-2.037	Highly Destabilizing	0.845	D	0.641	neutral	None	None	None	None	N
S/F	0.1902	likely_benign	0.2071	benign	-0.974	Destabilizing	0.994	D	0.772	deleterious	N	0.457105056	None	None	N
S/G	0.1561	likely_benign	0.1824	benign	-1.711	Destabilizing	0.916	D	0.632	neutral	None	None	None	None	N
S/H	0.5691	likely_pathogenic	0.6151	pathogenic	-1.829	Destabilizing	0.997	D	0.726	prob.delet.	None	None	None	None	N
S/I	0.2937	likely_benign	0.3251	benign	-0.466	Destabilizing	0.987	D	0.759	deleterious	None	None	None	None	N
S/K	0.8999	likely_pathogenic	0.9109	pathogenic	-0.848	Destabilizing	0.033	N	0.457	neutral	None	None	None	None	N
S/L	0.094	likely_benign	0.1051	benign	-0.466	Destabilizing	0.916	D	0.726	prob.delet.	None	None	None	None	N
S/M	0.1513	likely_benign	0.154	benign	-0.768	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
S/N	0.4173	ambiguous	0.4709	ambiguous	-1.529	Destabilizing	0.916	D	0.659	neutral	None	None	None	None	N
S/P	0.9892	likely_pathogenic	0.9923	pathogenic	-0.736	Destabilizing	0.983	D	0.717	prob.delet.	N	0.515895407	None	None	N
S/Q	0.6713	likely_pathogenic	0.6948	pathogenic	-1.242	Destabilizing	0.975	D	0.699	prob.neutral	None	None	None	None	N
S/R	0.8255	likely_pathogenic	0.8532	pathogenic	-1.131	Destabilizing	0.95	D	0.707	prob.neutral	None	None	None	None	N
S/T	0.1178	likely_benign	0.126	benign	-1.166	Destabilizing	0.892	D	0.623	neutral	N	0.498546247	None	None	N
S/V	0.2589	likely_benign	0.2762	benign	-0.736	Destabilizing	0.975	D	0.726	prob.delet.	None	None	None	None	N
S/W	0.4041	ambiguous	0.4555	ambiguous	-1.287	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
S/Y	0.2189	likely_benign	0.2485	benign	-0.894	Destabilizing	0.994	D	0.771	deleterious	N	0.482635432	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.