TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20512	61759;61760;61761	chr2:178590191;178590190;178590189	chr2:179454918;179454917;179454916
N2AB	18871	56836;56837;56838	chr2:178590191;178590190;178590189	chr2:179454918;179454917;179454916
N2A	17944	54055;54056;54057	chr2:178590191;178590190;178590189	chr2:179454918;179454917;179454916
N2B	11447	34564;34565;34566	chr2:178590191;178590190;178590189	chr2:179454918;179454917;179454916
Novex-1	11572	34939;34940;34941	chr2:178590191;178590190;178590189	chr2:179454918;179454917;179454916
Novex-2	11639	35140;35141;35142	chr2:178590191;178590190;178590189	chr2:179454918;179454917;179454916
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-121
• Domain position: 34
• Structural Position: 50
• Q(SASA): 0.2793
• 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
K/N	None	None	0.993	N	0.671	0.339	0.199424873507	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/R	rs2049906608	None	0.235	N	0.379	0.163	0.198526703765	gnomAD-4.0.0	1.60064E-06	None	None	None	None	N	None	0	0	None	0	2.77963E-05	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
K/A	0.9146	likely_pathogenic	0.9508	pathogenic	-1.072	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
K/C	0.8537	likely_pathogenic	0.8948	pathogenic	-1.06	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/D	0.9838	likely_pathogenic	0.9911	pathogenic	-0.331	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
K/E	0.8342	likely_pathogenic	0.9034	pathogenic	-0.17	Destabilizing	0.977	D	0.486	neutral	D	0.530437582	None	None	N
K/F	0.9453	likely_pathogenic	0.9576	pathogenic	-0.779	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/G	0.9543	likely_pathogenic	0.9738	pathogenic	-1.47	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
K/H	0.6075	likely_pathogenic	0.6499	pathogenic	-1.789	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
K/I	0.777	likely_pathogenic	0.864	pathogenic	-0.012	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
K/L	0.7806	likely_pathogenic	0.8491	pathogenic	-0.012	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	N
K/M	0.5969	likely_pathogenic	0.705	pathogenic	-0.06	Destabilizing	1.0	D	0.794	deleterious	N	0.507306897	None	None	N
K/N	0.9388	likely_pathogenic	0.9655	pathogenic	-0.764	Destabilizing	0.993	D	0.671	neutral	N	0.495950592	None	None	N
K/P	0.9953	likely_pathogenic	0.9966	pathogenic	-0.338	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
K/Q	0.4616	ambiguous	0.5467	ambiguous	-0.787	Destabilizing	0.993	D	0.655	neutral	N	0.503179067	None	None	N
K/R	0.0873	likely_benign	0.084	benign	-0.689	Destabilizing	0.235	N	0.379	neutral	N	0.490363907	None	None	N
K/S	0.9379	likely_pathogenic	0.9641	pathogenic	-1.556	Destabilizing	0.983	D	0.564	neutral	None	None	None	None	N
K/T	0.84	likely_pathogenic	0.9117	pathogenic	-1.159	Destabilizing	0.997	D	0.713	prob.delet.	N	0.511826348	None	None	N
K/V	0.7232	likely_pathogenic	0.8075	pathogenic	-0.338	Destabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
K/W	0.9248	likely_pathogenic	0.9266	pathogenic	-0.597	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/Y	0.8422	likely_pathogenic	0.8681	pathogenic	-0.284	Destabilizing	0.999	D	0.823	deleterious	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.