TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22809	68650;68651;68652	chr2:178578090;178578089;178578088	chr2:179442817;179442816;179442815
N2AB	21168	63727;63728;63729	chr2:178578090;178578089;178578088	chr2:179442817;179442816;179442815
N2A	20241	60946;60947;60948	chr2:178578090;178578089;178578088	chr2:179442817;179442816;179442815
N2B	13744	41455;41456;41457	chr2:178578090;178578089;178578088	chr2:179442817;179442816;179442815
Novex-1	13869	41830;41831;41832	chr2:178578090;178578089;178578088	chr2:179442817;179442816;179442815
Novex-2	13936	42031;42032;42033	chr2:178578090;178578089;178578088	chr2:179442817;179442816;179442815
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-53
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.3637
• 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/S	None	None	0.904	N	0.421	0.156	0.176091768786	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.095	likely_benign	0.095	benign	-0.72	Destabilizing	0.489	N	0.473	neutral	N	0.461761514	None	None	N
T/C	0.4088	ambiguous	0.4161	ambiguous	-0.452	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	N
T/D	0.5372	ambiguous	0.5565	ambiguous	0.424	Stabilizing	0.993	D	0.589	neutral	None	None	None	None	N
T/E	0.3721	ambiguous	0.3861	ambiguous	0.411	Stabilizing	0.978	D	0.548	neutral	None	None	None	None	N
T/F	0.2984	likely_benign	0.3115	benign	-0.982	Destabilizing	0.956	D	0.661	neutral	None	None	None	None	N
T/G	0.3093	likely_benign	0.3105	benign	-0.931	Destabilizing	0.978	D	0.55	neutral	None	None	None	None	N
T/H	0.3054	likely_benign	0.3268	benign	-1.067	Destabilizing	0.998	D	0.672	neutral	None	None	None	None	N
T/I	0.1527	likely_benign	0.1537	benign	-0.261	Destabilizing	0.058	N	0.277	neutral	N	0.40562023	None	None	N
T/K	0.3039	likely_benign	0.3284	benign	-0.38	Destabilizing	0.978	D	0.552	neutral	None	None	None	None	N
T/L	0.0915	likely_benign	0.0967	benign	-0.261	Destabilizing	0.559	D	0.465	neutral	None	None	None	None	N
T/M	0.0805	likely_benign	0.0784	benign	-0.174	Destabilizing	0.978	D	0.613	neutral	None	None	None	None	N
T/N	0.1532	likely_benign	0.1624	benign	-0.316	Destabilizing	0.99	D	0.526	neutral	N	0.433286834	None	None	N
T/P	0.2682	likely_benign	0.2874	benign	-0.383	Destabilizing	0.99	D	0.602	neutral	N	0.471959865	None	None	N
T/Q	0.2369	likely_benign	0.2441	benign	-0.429	Destabilizing	0.993	D	0.604	neutral	None	None	None	None	N
T/R	0.2554	likely_benign	0.2859	benign	-0.17	Destabilizing	0.978	D	0.602	neutral	None	None	None	None	N
T/S	0.1276	likely_benign	0.1336	benign	-0.657	Destabilizing	0.904	D	0.421	neutral	N	0.438327294	None	None	N
T/V	0.1133	likely_benign	0.1163	benign	-0.383	Destabilizing	0.008	N	0.122	neutral	None	None	None	None	N
T/W	0.6032	likely_pathogenic	0.6362	pathogenic	-0.928	Destabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	N
T/Y	0.3416	ambiguous	0.3683	ambiguous	-0.661	Destabilizing	0.978	D	0.665	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.