TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27087	81484;81485;81486	chr2:178564873;178564872;178564871	chr2:179429600;179429599;179429598
N2AB	25446	76561;76562;76563	chr2:178564873;178564872;178564871	chr2:179429600;179429599;179429598
N2A	24519	73780;73781;73782	chr2:178564873;178564872;178564871	chr2:179429600;179429599;179429598
N2B	18022	54289;54290;54291	chr2:178564873;178564872;178564871	chr2:179429600;179429599;179429598
Novex-1	18147	54664;54665;54666	chr2:178564873;178564872;178564871	chr2:179429600;179429599;179429598
Novex-2	18214	54865;54866;54867	chr2:178564873;178564872;178564871	chr2:179429600;179429599;179429598
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-85
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.5199
• 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
D/N	None	None	0.939	N	0.527	0.282	0.18995819373	gnomAD-4.0.0	1.59443E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03251E-05

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
D/A	0.2822	likely_benign	0.2758	benign	-0.213	Destabilizing	0.885	D	0.489	neutral	N	0.491741219	None	None	N
D/C	0.6587	likely_pathogenic	0.6331	pathogenic	0.185	Stabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
D/E	0.1315	likely_benign	0.1371	benign	-0.666	Destabilizing	0.17	N	0.238	neutral	N	0.487601321	None	None	N
D/F	0.6018	likely_pathogenic	0.6018	pathogenic	-0.839	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
D/G	0.1997	likely_benign	0.2003	benign	-0.399	Destabilizing	0.885	D	0.514	neutral	N	0.475763331	None	None	N
D/H	0.371	ambiguous	0.3529	ambiguous	-1.076	Destabilizing	0.999	D	0.592	neutral	N	0.472978627	None	None	N
D/I	0.4803	ambiguous	0.4822	ambiguous	0.225	Stabilizing	0.993	D	0.717	prob.delet.	None	None	None	None	N
D/K	0.5042	ambiguous	0.4898	ambiguous	0.255	Stabilizing	0.953	D	0.545	neutral	None	None	None	None	N
D/L	0.4787	ambiguous	0.4696	ambiguous	0.225	Stabilizing	0.986	D	0.704	prob.neutral	None	None	None	None	N
D/M	0.6278	likely_pathogenic	0.6143	pathogenic	0.639	Stabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
D/N	0.1019	likely_benign	0.1031	benign	0.111	Stabilizing	0.939	D	0.527	neutral	N	0.501413194	None	None	N
D/P	0.9371	likely_pathogenic	0.9486	pathogenic	0.101	Stabilizing	0.993	D	0.622	neutral	None	None	None	None	N
D/Q	0.3796	ambiguous	0.3545	ambiguous	0.082	Stabilizing	0.986	D	0.589	neutral	None	None	None	None	N
D/R	0.5772	likely_pathogenic	0.5504	ambiguous	0.033	Stabilizing	0.986	D	0.673	neutral	None	None	None	None	N
D/S	0.1525	likely_benign	0.1501	benign	-0.033	Destabilizing	0.386	N	0.272	neutral	None	None	None	None	N
D/T	0.2342	likely_benign	0.2287	benign	0.117	Stabilizing	0.91	D	0.54	neutral	None	None	None	None	N
D/V	0.3095	likely_benign	0.307	benign	0.101	Stabilizing	0.982	D	0.705	prob.neutral	D	0.524088615	None	None	N
D/W	0.8888	likely_pathogenic	0.8862	pathogenic	-0.948	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
D/Y	0.2531	likely_benign	0.2491	benign	-0.636	Destabilizing	0.999	D	0.705	prob.neutral	N	0.489437041	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.