TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32631	98116;98117;98118	chr2:178540275;178540274;178540273	chr2:179405002;179405001;179405000
N2AB	30990	93193;93194;93195	chr2:178540275;178540274;178540273	chr2:179405002;179405001;179405000
N2A	30063	90412;90413;90414	chr2:178540275;178540274;178540273	chr2:179405002;179405001;179405000
N2B	23566	70921;70922;70923	chr2:178540275;178540274;178540273	chr2:179405002;179405001;179405000
Novex-1	23691	71296;71297;71298	chr2:178540275;178540274;178540273	chr2:179405002;179405001;179405000
Novex-2	23758	71497;71498;71499	chr2:178540275;178540274;178540273	chr2:179405002;179405001;179405000
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-126
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.3898
• 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
K/I	rs944963846	0.519	0.852	N	0.561	0.258	0.419835214384	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
K/I	rs944963846	0.519	0.852	N	0.561	0.258	0.419835214384	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/I	rs944963846	0.519	0.852	N	0.561	0.258	0.419835214384	gnomAD-4.0.0	3.84309E-06	None	None	None	None	I	None	5.07408E-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
K/A	0.2924	likely_benign	0.3229	benign	0.071	Stabilizing	0.079	N	0.144	neutral	None	None	None	None	I
K/C	0.6885	likely_pathogenic	0.7062	pathogenic	-0.243	Destabilizing	0.999	D	0.524	neutral	None	None	None	None	I
K/D	0.5866	likely_pathogenic	0.6307	pathogenic	-0.113	Destabilizing	0.991	D	0.483	neutral	None	None	None	None	I
K/E	0.2049	likely_benign	0.2429	benign	-0.122	Destabilizing	0.959	D	0.435	neutral	N	0.395227091	None	None	I
K/F	0.7936	likely_pathogenic	0.8257	pathogenic	-0.227	Destabilizing	0.991	D	0.557	neutral	None	None	None	None	I
K/G	0.5021	ambiguous	0.5473	ambiguous	-0.081	Destabilizing	0.884	D	0.541	neutral	None	None	None	None	I
K/H	0.38	ambiguous	0.4001	ambiguous	-0.227	Destabilizing	0.999	D	0.461	neutral	None	None	None	None	I
K/I	0.3712	ambiguous	0.3993	ambiguous	0.387	Stabilizing	0.852	D	0.561	neutral	N	0.488582756	None	None	I
K/L	0.3669	ambiguous	0.4092	ambiguous	0.387	Stabilizing	0.759	D	0.507	neutral	None	None	None	None	I
K/M	0.2794	likely_benign	0.322	benign	0.099	Stabilizing	0.991	D	0.478	neutral	None	None	None	None	I
K/N	0.5065	ambiguous	0.5498	ambiguous	0.242	Stabilizing	0.996	D	0.41	neutral	N	0.456008978	None	None	I
K/P	0.3852	ambiguous	0.4124	ambiguous	0.306	Stabilizing	0.991	D	0.497	neutral	None	None	None	None	I
K/Q	0.1682	likely_benign	0.1808	benign	0.07	Stabilizing	0.996	D	0.443	neutral	N	0.490140194	None	None	I
K/R	0.0844	likely_benign	0.088	benign	0.047	Stabilizing	0.959	D	0.437	neutral	N	0.43857801	None	None	I
K/S	0.452	ambiguous	0.4904	ambiguous	-0.175	Destabilizing	0.884	D	0.395	neutral	None	None	None	None	I
K/T	0.216	likely_benign	0.2381	benign	-0.057	Destabilizing	0.92	D	0.503	neutral	N	0.470034281	None	None	I
K/V	0.2855	likely_benign	0.3096	benign	0.306	Stabilizing	0.079	N	0.159	neutral	None	None	None	None	I
K/W	0.7943	likely_pathogenic	0.8383	pathogenic	-0.297	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
K/Y	0.6941	likely_pathogenic	0.7396	pathogenic	0.063	Stabilizing	0.997	D	0.551	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.