TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23697	71314;71315;71316	chr2:178575043;178575042;178575041	chr2:179439770;179439769;179439768
N2AB	22056	66391;66392;66393	chr2:178575043;178575042;178575041	chr2:179439770;179439769;179439768
N2A	21129	63610;63611;63612	chr2:178575043;178575042;178575041	chr2:179439770;179439769;179439768
N2B	14632	44119;44120;44121	chr2:178575043;178575042;178575041	chr2:179439770;179439769;179439768
Novex-1	14757	44494;44495;44496	chr2:178575043;178575042;178575041	chr2:179439770;179439769;179439768
Novex-2	14824	44695;44696;44697	chr2:178575043;178575042;178575041	chr2:179439770;179439769;179439768
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: Ig-130
• Domain position: 61
• Structural Position: 145
• Q(SASA): 0.2575
• 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	None	None	None	N	0.189	0.11	0.368554958709	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85936E-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	0.114	likely_benign	0.1237	benign	-0.958	Destabilizing	0.019	N	0.257	neutral	N	0.443378902	None	None	N
V/C	0.4487	ambiguous	0.4714	ambiguous	-0.829	Destabilizing	0.667	D	0.428	neutral	None	None	None	None	N
V/D	0.2435	likely_benign	0.2492	benign	-0.637	Destabilizing	0.175	N	0.483	neutral	N	0.433316624	None	None	N
V/E	0.1874	likely_benign	0.1911	benign	-0.731	Destabilizing	0.104	N	0.443	neutral	None	None	None	None	N
V/F	0.1143	likely_benign	0.133	benign	-1.101	Destabilizing	0.427	N	0.483	neutral	N	0.457348277	None	None	N
V/G	0.1291	likely_benign	0.1403	benign	-1.137	Destabilizing	0.175	N	0.447	neutral	N	0.453942613	None	None	N
V/H	0.2945	likely_benign	0.3011	benign	-0.612	Destabilizing	0.859	D	0.487	neutral	None	None	None	None	N
V/I	0.0666	likely_benign	0.0693	benign	-0.618	Destabilizing	None	N	0.189	neutral	N	0.47035486	None	None	N
V/K	0.153	likely_benign	0.1528	benign	-0.628	Destabilizing	0.002	N	0.146	neutral	None	None	None	None	N
V/L	0.0894	likely_benign	0.1008	benign	-0.618	Destabilizing	None	N	0.185	neutral	N	0.42600665	None	None	N
V/M	0.0813	likely_benign	0.0885	benign	-0.428	Destabilizing	0.497	N	0.351	neutral	None	None	None	None	N
V/N	0.1267	likely_benign	0.1335	benign	-0.392	Destabilizing	0.22	N	0.493	neutral	None	None	None	None	N
V/P	0.6257	likely_pathogenic	0.6605	pathogenic	-0.696	Destabilizing	0.364	N	0.48	neutral	None	None	None	None	N
V/Q	0.1443	likely_benign	0.1406	benign	-0.696	Destabilizing	0.22	N	0.48	neutral	None	None	None	None	N
V/R	0.1513	likely_benign	0.1518	benign	-0.053	Destabilizing	0.001	N	0.257	neutral	None	None	None	None	N
V/S	0.1007	likely_benign	0.1069	benign	-0.852	Destabilizing	0.055	N	0.404	neutral	None	None	None	None	N
V/T	0.0852	likely_benign	0.0966	benign	-0.847	Destabilizing	None	N	0.147	neutral	None	None	None	None	N
V/W	0.6596	likely_pathogenic	0.6951	pathogenic	-1.132	Destabilizing	0.958	D	0.482	neutral	None	None	None	None	N
V/Y	0.3608	ambiguous	0.3769	ambiguous	-0.832	Destabilizing	0.667	D	0.453	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.