TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24822	74689;74690;74691	chr2:178571668;178571667;178571666	chr2:179436395;179436394;179436393
N2AB	23181	69766;69767;69768	chr2:178571668;178571667;178571666	chr2:179436395;179436394;179436393
N2A	22254	66985;66986;66987	chr2:178571668;178571667;178571666	chr2:179436395;179436394;179436393
N2B	15757	47494;47495;47496	chr2:178571668;178571667;178571666	chr2:179436395;179436394;179436393
Novex-1	15882	47869;47870;47871	chr2:178571668;178571667;178571666	chr2:179436395;179436394;179436393
Novex-2	15949	48070;48071;48072	chr2:178571668;178571667;178571666	chr2:179436395;179436394;179436393
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-68
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.2739
• 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
T/R	rs1479629836	None	0.967	N	0.627	0.393	0.509346181843	gnomAD-4.0.0	4.7761E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57859E-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
T/A	0.2707	likely_benign	0.2583	benign	-1.077	Destabilizing	0.63	D	0.447	neutral	D	0.528085294	None	None	N
T/C	0.7049	likely_pathogenic	0.695	pathogenic	-0.763	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
T/D	0.673	likely_pathogenic	0.6632	pathogenic	-0.991	Destabilizing	0.975	D	0.559	neutral	None	None	None	None	N
T/E	0.7907	likely_pathogenic	0.7715	pathogenic	-0.902	Destabilizing	0.975	D	0.565	neutral	None	None	None	None	N
T/F	0.7225	likely_pathogenic	0.7189	pathogenic	-0.928	Destabilizing	0.987	D	0.662	neutral	None	None	None	None	N
T/G	0.4475	ambiguous	0.413	ambiguous	-1.413	Destabilizing	0.845	D	0.491	neutral	None	None	None	None	N
T/H	0.5793	likely_pathogenic	0.5671	pathogenic	-1.635	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	N
T/I	0.8365	likely_pathogenic	0.83	pathogenic	-0.24	Destabilizing	0.983	D	0.623	neutral	N	0.497785287	None	None	N
T/K	0.6202	likely_pathogenic	0.5968	pathogenic	-0.828	Destabilizing	0.967	D	0.565	neutral	N	0.47717259	None	None	N
T/L	0.3376	likely_benign	0.3219	benign	-0.24	Destabilizing	0.916	D	0.507	neutral	None	None	None	None	N
T/M	0.2055	likely_benign	0.194	benign	0.01	Stabilizing	0.999	D	0.606	neutral	None	None	None	None	N
T/N	0.2675	likely_benign	0.2698	benign	-1.114	Destabilizing	0.975	D	0.555	neutral	None	None	None	None	N
T/P	0.8985	likely_pathogenic	0.8813	pathogenic	-0.487	Destabilizing	0.983	D	0.622	neutral	D	0.524283333	None	None	N
T/Q	0.577	likely_pathogenic	0.5612	ambiguous	-1.151	Destabilizing	0.975	D	0.616	neutral	None	None	None	None	N
T/R	0.5795	likely_pathogenic	0.5471	ambiguous	-0.736	Destabilizing	0.967	D	0.627	neutral	N	0.520561889	None	None	N
T/S	0.1445	likely_benign	0.1432	benign	-1.357	Destabilizing	0.099	N	0.212	neutral	N	0.425014067	None	None	N
T/V	0.6403	likely_pathogenic	0.6262	pathogenic	-0.487	Destabilizing	0.916	D	0.474	neutral	None	None	None	None	N
T/W	0.9325	likely_pathogenic	0.925	pathogenic	-0.928	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
T/Y	0.7199	likely_pathogenic	0.7114	pathogenic	-0.647	Destabilizing	0.996	D	0.668	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.