TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23225	69898;69899;69900	chr2:178576571;178576570;178576569	chr2:179441298;179441297;179441296
N2AB	21584	64975;64976;64977	chr2:178576571;178576570;178576569	chr2:179441298;179441297;179441296
N2A	20657	62194;62195;62196	chr2:178576571;178576570;178576569	chr2:179441298;179441297;179441296
N2B	14160	42703;42704;42705	chr2:178576571;178576570;178576569	chr2:179441298;179441297;179441296
Novex-1	14285	43078;43079;43080	chr2:178576571;178576570;178576569	chr2:179441298;179441297;179441296
Novex-2	14352	43279;43280;43281	chr2:178576571;178576570;178576569	chr2:179441298;179441297;179441296
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-56
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.3234
• Predicted PPI site: I

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
P/S	None	None	0.997	N	0.745	0.371	0.240491677333	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	6.33473E-05	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
P/A	0.0679	likely_benign	0.0762	benign	-1.192	Destabilizing	0.977	D	0.627	neutral	N	0.480861758	None	None	I
P/C	0.4039	ambiguous	0.4553	ambiguous	-0.871	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
P/D	0.7842	likely_pathogenic	0.8162	pathogenic	-0.805	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	I
P/E	0.5579	ambiguous	0.5999	pathogenic	-0.887	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	I
P/F	0.3593	ambiguous	0.3911	ambiguous	-1.184	Destabilizing	0.99	D	0.815	deleterious	None	None	None	None	I
P/G	0.4658	ambiguous	0.5121	ambiguous	-1.394	Destabilizing	0.998	D	0.704	prob.neutral	None	None	None	None	I
P/H	0.2864	likely_benign	0.3167	benign	-0.843	Destabilizing	0.998	D	0.845	deleterious	D	0.522896846	None	None	I
P/I	0.3164	likely_benign	0.3574	ambiguous	-0.778	Destabilizing	0.995	D	0.839	deleterious	None	None	None	None	I
P/K	0.6017	likely_pathogenic	0.6374	pathogenic	-0.856	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
P/L	0.1454	likely_benign	0.1695	benign	-0.778	Destabilizing	0.987	D	0.739	prob.delet.	N	0.511398729	None	None	I
P/M	0.3246	likely_benign	0.3741	ambiguous	-0.579	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/N	0.6249	likely_pathogenic	0.6714	pathogenic	-0.574	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
P/Q	0.2781	likely_benign	0.3203	benign	-0.867	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	I
P/R	0.3846	ambiguous	0.4286	ambiguous	-0.259	Destabilizing	0.997	D	0.833	deleterious	N	0.518262037	None	None	I
P/S	0.162	likely_benign	0.1846	benign	-1.04	Destabilizing	0.997	D	0.745	deleterious	N	0.494624373	None	None	I
P/T	0.1603	likely_benign	0.2	benign	-1.025	Destabilizing	0.997	D	0.775	deleterious	N	0.515388428	None	None	I
P/V	0.1885	likely_benign	0.2175	benign	-0.881	Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	I
P/W	0.6354	likely_pathogenic	0.6748	pathogenic	-1.213	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	I
P/Y	0.421	ambiguous	0.452	ambiguous	-0.951	Destabilizing	0.289	N	0.647	neutral	None	None	None	None	I

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.