TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27315	82168;82169;82170	chr2:178564189;178564188;178564187	chr2:179428916;179428915;179428914
N2AB	25674	77245;77246;77247	chr2:178564189;178564188;178564187	chr2:179428916;179428915;179428914
N2A	24747	74464;74465;74466	chr2:178564189;178564188;178564187	chr2:179428916;179428915;179428914
N2B	18250	54973;54974;54975	chr2:178564189;178564188;178564187	chr2:179428916;179428915;179428914
Novex-1	18375	55348;55349;55350	chr2:178564189;178564188;178564187	chr2:179428916;179428915;179428914
Novex-2	18442	55549;55550;55551	chr2:178564189;178564188;178564187	chr2:179428916;179428915;179428914
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-140
• Domain position: 38
• Structural Position: 56
• Q(SASA): 0.1398
• 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
E/Q	None	None	0.942	N	0.697	0.351	0.505946769237	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	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
E/A	0.1003	likely_benign	0.099	benign	-0.418	Destabilizing	0.822	D	0.662	neutral	N	0.492404734	None	None	N
E/C	0.5895	likely_pathogenic	0.604	pathogenic	-0.073	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
E/D	0.0845	likely_benign	0.0835	benign	-0.34	Destabilizing	0.006	N	0.284	neutral	D	0.534270265	None	None	N
E/F	0.421	ambiguous	0.428	ambiguous	-0.226	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
E/G	0.1182	likely_benign	0.1206	benign	-0.622	Destabilizing	0.822	D	0.685	prob.neutral	D	0.529400166	None	None	N
E/H	0.2856	likely_benign	0.2932	benign	-0.003	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
E/I	0.1287	likely_benign	0.1315	benign	0.089	Stabilizing	0.978	D	0.863	deleterious	None	None	None	None	N
E/K	0.1103	likely_benign	0.1205	benign	0.351	Stabilizing	0.822	D	0.561	neutral	N	0.487262946	None	None	N
E/L	0.1746	likely_benign	0.1747	benign	0.089	Stabilizing	0.978	D	0.836	deleterious	None	None	None	None	N
E/M	0.2195	likely_benign	0.2307	benign	0.174	Stabilizing	0.998	D	0.844	deleterious	None	None	None	None	N
E/N	0.1302	likely_benign	0.1294	benign	-0.053	Destabilizing	0.915	D	0.691	prob.neutral	None	None	None	None	N
E/P	0.2431	likely_benign	0.2261	benign	-0.06	Destabilizing	0.978	D	0.825	deleterious	None	None	None	None	N
E/Q	0.1088	likely_benign	0.1142	benign	-0.003	Destabilizing	0.942	D	0.697	prob.neutral	N	0.492151244	None	None	N
E/R	0.191	likely_benign	0.2065	benign	0.548	Stabilizing	0.978	D	0.74	deleterious	None	None	None	None	N
E/S	0.1311	likely_benign	0.1318	benign	-0.195	Destabilizing	0.754	D	0.565	neutral	None	None	None	None	N
E/T	0.122	likely_benign	0.1214	benign	-0.021	Destabilizing	0.956	D	0.759	deleterious	None	None	None	None	N
E/V	0.0906	likely_benign	0.0897	benign	-0.06	Destabilizing	0.971	D	0.805	deleterious	N	0.485683238	None	None	N
E/W	0.6974	likely_pathogenic	0.7098	pathogenic	-0.046	Destabilizing	0.998	D	0.836	deleterious	None	None	None	None	N
E/Y	0.3139	likely_benign	0.3266	benign	0.025	Stabilizing	0.998	D	0.846	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.