TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16611	50056;50057;50058	chr2:178612890;178612889;178612888	chr2:179477617;179477616;179477615
N2AB	14970	45133;45134;45135	chr2:178612890;178612889;178612888	chr2:179477617;179477616;179477615
N2A	14043	42352;42353;42354	chr2:178612890;178612889;178612888	chr2:179477617;179477616;179477615
N2B	7546	22861;22862;22863	chr2:178612890;178612889;178612888	chr2:179477617;179477616;179477615
Novex-1	7671	23236;23237;23238	chr2:178612890;178612889;178612888	chr2:179477617;179477616;179477615
Novex-2	7738	23437;23438;23439	chr2:178612890;178612889;178612888	chr2:179477617;179477616;179477615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-8
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.3955
• 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
L/F	rs758670411	-0.954	None	N	0.168	0.055	0.220303561663	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	1.13122E-04	None	0	None	0	0	0
L/F	rs758670411	-0.954	None	N	0.168	0.055	0.220303561663	gnomAD-4.0.0	1.59379E-06	None	None	None	None	N	None	0	0	None	0	2.79298E-05	None	0	0	0	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
L/A	0.1831	likely_benign	0.1687	benign	-1.276	Destabilizing	0.016	N	0.409	neutral	None	None	None	None	N
L/C	0.4028	ambiguous	0.3511	ambiguous	-0.697	Destabilizing	0.676	D	0.537	neutral	None	None	None	None	N
L/D	0.3755	ambiguous	0.381	ambiguous	-0.795	Destabilizing	0.214	N	0.627	neutral	None	None	None	None	N
L/E	0.2233	likely_benign	0.2442	benign	-0.833	Destabilizing	0.038	N	0.581	neutral	None	None	None	None	N
L/F	0.0957	likely_benign	0.0914	benign	-0.955	Destabilizing	None	N	0.168	neutral	N	0.465407492	None	None	N
L/G	0.4333	ambiguous	0.4175	ambiguous	-1.543	Destabilizing	0.072	N	0.575	neutral	None	None	None	None	N
L/H	0.149	likely_benign	0.1544	benign	-0.782	Destabilizing	0.356	N	0.575	neutral	None	None	None	None	N
L/I	0.0747	likely_benign	0.0649	benign	-0.643	Destabilizing	0.006	N	0.388	neutral	None	None	None	None	N
L/K	0.2776	likely_benign	0.3103	benign	-0.908	Destabilizing	None	N	0.419	neutral	None	None	None	None	N
L/M	0.1044	likely_benign	0.0931	benign	-0.497	Destabilizing	0.171	N	0.527	neutral	N	0.477853043	None	None	N
L/N	0.2136	likely_benign	0.1916	benign	-0.63	Destabilizing	0.214	N	0.609	neutral	None	None	None	None	N
L/P	0.3166	likely_benign	0.3165	benign	-0.821	Destabilizing	0.356	N	0.604	neutral	None	None	None	None	N
L/Q	0.124	likely_benign	0.1345	benign	-0.837	Destabilizing	0.12	N	0.61	neutral	None	None	None	None	N
L/R	0.1966	likely_benign	0.2417	benign	-0.291	Destabilizing	0.12	N	0.626	neutral	None	None	None	None	N
L/S	0.162	likely_benign	0.1434	benign	-1.144	Destabilizing	0.029	N	0.523	neutral	N	0.443365853	None	None	N
L/T	0.1304	likely_benign	0.1177	benign	-1.072	Destabilizing	0.038	N	0.459	neutral	None	None	None	None	N
L/V	0.0728	likely_benign	0.0646	benign	-0.821	Destabilizing	None	N	0.163	neutral	N	0.399877837	None	None	N
L/W	0.2232	likely_benign	0.2368	benign	-1.004	Destabilizing	0.612	D	0.565	neutral	D	0.543102491	None	None	N
L/Y	0.241	likely_benign	0.2385	benign	-0.793	Destabilizing	0.038	N	0.463	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.