TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29663	89212;89213;89214	chr2:178554124;178554123;178554122	chr2:179418851;179418850;179418849
N2AB	28022	84289;84290;84291	chr2:178554124;178554123;178554122	chr2:179418851;179418850;179418849
N2A	27095	81508;81509;81510	chr2:178554124;178554123;178554122	chr2:179418851;179418850;179418849
N2B	20598	62017;62018;62019	chr2:178554124;178554123;178554122	chr2:179418851;179418850;179418849
Novex-1	20723	62392;62393;62394	chr2:178554124;178554123;178554122	chr2:179418851;179418850;179418849
Novex-2	20790	62593;62594;62595	chr2:178554124;178554123;178554122	chr2:179418851;179418850;179418849
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: Fn3-104
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3116
• 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
S/R	None	None	0.942	N	0.636	0.359	0.283761946502	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	6.33473E-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
S/A	0.1522	likely_benign	0.1658	benign	-0.45	Destabilizing	0.717	D	0.653	neutral	None	None	None	None	I
S/C	0.1027	likely_benign	0.118	benign	-0.199	Destabilizing	0.997	D	0.649	neutral	N	0.491958709	None	None	I
S/D	0.7753	likely_pathogenic	0.8552	pathogenic	-0.347	Destabilizing	0.754	D	0.629	neutral	None	None	None	None	I
S/E	0.8773	likely_pathogenic	0.9057	pathogenic	-0.443	Destabilizing	0.86	D	0.658	neutral	None	None	None	None	I
S/F	0.594	likely_pathogenic	0.688	pathogenic	-1.073	Destabilizing	0.993	D	0.709	prob.delet.	None	None	None	None	I
S/G	0.2002	likely_benign	0.2691	benign	-0.563	Destabilizing	0.489	N	0.618	neutral	N	0.47740181	None	None	I
S/H	0.5575	ambiguous	0.6604	pathogenic	-1.156	Destabilizing	0.956	D	0.621	neutral	None	None	None	None	I
S/I	0.5089	ambiguous	0.6036	pathogenic	-0.278	Destabilizing	0.971	D	0.707	prob.neutral	N	0.496616291	None	None	I
S/K	0.9006	likely_pathogenic	0.9303	pathogenic	-0.551	Destabilizing	0.754	D	0.659	neutral	None	None	None	None	I
S/L	0.2711	likely_benign	0.3233	benign	-0.278	Destabilizing	0.978	D	0.671	neutral	None	None	None	None	I
S/M	0.3632	ambiguous	0.4343	ambiguous	0.207	Stabilizing	0.998	D	0.633	neutral	None	None	None	None	I
S/N	0.1659	likely_benign	0.2424	benign	-0.28	Destabilizing	0.006	N	0.399	neutral	N	0.480816214	None	None	I
S/P	0.9798	likely_pathogenic	0.9868	pathogenic	-0.307	Destabilizing	0.978	D	0.635	neutral	None	None	None	None	I
S/Q	0.7213	likely_pathogenic	0.7891	pathogenic	-0.624	Destabilizing	0.956	D	0.677	prob.neutral	None	None	None	None	I
S/R	0.8402	likely_pathogenic	0.8845	pathogenic	-0.27	Destabilizing	0.942	D	0.636	neutral	N	0.496892552	None	None	I
S/T	0.1897	likely_benign	0.256	benign	-0.348	Destabilizing	0.822	D	0.635	neutral	N	0.484512743	None	None	I
S/V	0.4524	ambiguous	0.5133	ambiguous	-0.307	Destabilizing	0.978	D	0.701	prob.neutral	None	None	None	None	I
S/W	0.7439	likely_pathogenic	0.8027	pathogenic	-1.061	Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	I
S/Y	0.5195	ambiguous	0.5992	pathogenic	-0.788	Destabilizing	0.993	D	0.711	prob.delet.	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.