TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27120	81583;81584;81585	chr2:178564774;178564773;178564772	chr2:179429501;179429500;179429499
N2AB	25479	76660;76661;76662	chr2:178564774;178564773;178564772	chr2:179429501;179429500;179429499
N2A	24552	73879;73880;73881	chr2:178564774;178564773;178564772	chr2:179429501;179429500;179429499
N2B	18055	54388;54389;54390	chr2:178564774;178564773;178564772	chr2:179429501;179429500;179429499
Novex-1	18180	54763;54764;54765	chr2:178564774;178564773;178564772	chr2:179429501;179429500;179429499
Novex-2	18247	54964;54965;54966	chr2:178564774;178564773;178564772	chr2:179429501;179429500;179429499
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-85
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4012
• 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
V/I	rs1015972053	None	None	N	0.157	0.182	0.319402600006	gnomAD-4.0.0	7.53498E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.90129E-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
V/A	0.1546	likely_benign	0.1393	benign	-1.006	Destabilizing	None	N	0.117	neutral	N	0.481982071	None	None	N
V/C	0.4951	ambiguous	0.5056	ambiguous	-0.726	Destabilizing	0.667	D	0.318	neutral	None	None	None	None	N
V/D	0.4101	ambiguous	0.4037	ambiguous	-0.646	Destabilizing	0.175	N	0.318	neutral	N	0.485638452	None	None	N
V/E	0.2852	likely_benign	0.2701	benign	-0.665	Destabilizing	0.22	N	0.313	neutral	None	None	None	None	N
V/F	0.1583	likely_benign	0.1606	benign	-0.72	Destabilizing	0.175	N	0.387	neutral	N	0.497836958	None	None	N
V/G	0.1776	likely_benign	0.1736	benign	-1.269	Destabilizing	0.042	N	0.303	neutral	N	0.519193665	None	None	N
V/H	0.376	ambiguous	0.3829	ambiguous	-0.658	Destabilizing	0.859	D	0.333	neutral	None	None	None	None	N
V/I	0.0709	likely_benign	0.0746	benign	-0.408	Destabilizing	None	N	0.157	neutral	N	0.438692654	None	None	N
V/K	0.2436	likely_benign	0.2315	benign	-0.878	Destabilizing	0.22	N	0.299	neutral	None	None	None	None	N
V/L	0.1292	likely_benign	0.1318	benign	-0.408	Destabilizing	0.007	N	0.159	neutral	N	0.483502223	None	None	N
V/M	0.0982	likely_benign	0.0988	benign	-0.421	Destabilizing	0.025	N	0.158	neutral	None	None	None	None	N
V/N	0.1566	likely_benign	0.1597	benign	-0.727	Destabilizing	0.22	N	0.361	neutral	None	None	None	None	N
V/P	0.8836	likely_pathogenic	0.8856	pathogenic	-0.571	Destabilizing	0.364	N	0.335	neutral	None	None	None	None	N
V/Q	0.1993	likely_benign	0.1907	benign	-0.885	Destabilizing	0.667	D	0.394	neutral	None	None	None	None	N
V/R	0.2489	likely_benign	0.2369	benign	-0.347	Destabilizing	0.22	N	0.401	neutral	None	None	None	None	N
V/S	0.1532	likely_benign	0.1459	benign	-1.207	Destabilizing	0.011	N	0.259	neutral	None	None	None	None	N
V/T	0.1258	likely_benign	0.1167	benign	-1.12	Destabilizing	0.001	N	0.087	neutral	None	None	None	None	N
V/W	0.7314	likely_pathogenic	0.7419	pathogenic	-0.878	Destabilizing	0.958	D	0.354	neutral	None	None	None	None	N
V/Y	0.3773	ambiguous	0.3938	ambiguous	-0.583	Destabilizing	0.667	D	0.372	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.