TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28162	84709;84710;84711	chr2:178561648;178561647;178561646	chr2:179426375;179426374;179426373
N2AB	26521	79786;79787;79788	chr2:178561648;178561647;178561646	chr2:179426375;179426374;179426373
N2A	25594	77005;77006;77007	chr2:178561648;178561647;178561646	chr2:179426375;179426374;179426373
N2B	19097	57514;57515;57516	chr2:178561648;178561647;178561646	chr2:179426375;179426374;179426373
Novex-1	19222	57889;57890;57891	chr2:178561648;178561647;178561646	chr2:179426375;179426374;179426373
Novex-2	19289	58090;58091;58092	chr2:178561648;178561647;178561646	chr2:179426375;179426374;179426373
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-93
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.676
• 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
K/E	rs775599688	None	0.001	N	0.233	0.096	0.236278675362	gnomAD-4.0.0	1.60188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87652E-06	0	0
K/T	None	None	0.491	N	0.417	0.131	0.262662153117	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-05	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
K/A	0.2272	likely_benign	0.2177	benign	-0.169	Destabilizing	0.345	N	0.367	neutral	None	None	None	None	N
K/C	0.4496	ambiguous	0.4456	ambiguous	-0.208	Destabilizing	0.991	D	0.414	neutral	None	None	None	None	N
K/D	0.4782	ambiguous	0.4398	ambiguous	0.051	Stabilizing	0.209	N	0.38	neutral	None	None	None	None	N
K/E	0.1285	likely_benign	0.1157	benign	0.106	Stabilizing	0.001	N	0.233	neutral	N	0.432286756	None	None	N
K/F	0.5458	ambiguous	0.5156	ambiguous	-0.055	Destabilizing	0.901	D	0.428	neutral	None	None	None	None	N
K/G	0.3773	ambiguous	0.3769	ambiguous	-0.465	Destabilizing	0.345	N	0.37	neutral	None	None	None	None	N
K/H	0.1822	likely_benign	0.1664	benign	-0.819	Destabilizing	0.002	N	0.275	neutral	None	None	None	None	N
K/I	0.2259	likely_benign	0.2032	benign	0.56	Stabilizing	0.873	D	0.489	neutral	N	0.471037145	None	None	N
K/L	0.2413	likely_benign	0.2256	benign	0.56	Stabilizing	0.561	D	0.41	neutral	None	None	None	None	N
K/M	0.1721	likely_benign	0.1574	benign	0.339	Stabilizing	0.965	D	0.465	neutral	None	None	None	None	N
K/N	0.3084	likely_benign	0.2797	benign	-0.003	Destabilizing	0.285	N	0.344	neutral	N	0.505168362	None	None	N
K/P	0.9086	likely_pathogenic	0.9092	pathogenic	0.348	Stabilizing	0.722	D	0.493	neutral	None	None	None	None	N
K/Q	0.0963	likely_benign	0.0915	benign	-0.119	Destabilizing	0.005	N	0.245	neutral	N	0.412199486	None	None	N
K/R	0.0675	likely_benign	0.0682	benign	-0.356	Destabilizing	0.001	N	0.193	neutral	N	0.407985744	None	None	N
K/S	0.2716	likely_benign	0.2552	benign	-0.538	Destabilizing	0.345	N	0.37	neutral	None	None	None	None	N
K/T	0.1213	likely_benign	0.113	benign	-0.307	Destabilizing	0.491	N	0.417	neutral	N	0.417893307	None	None	N
K/V	0.1837	likely_benign	0.1685	benign	0.348	Stabilizing	0.722	D	0.459	neutral	None	None	None	None	N
K/W	0.5631	ambiguous	0.5535	ambiguous	-0.008	Destabilizing	0.991	D	0.412	neutral	None	None	None	None	N
K/Y	0.427	ambiguous	0.3989	ambiguous	0.293	Stabilizing	0.561	D	0.536	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.