TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35458	106597;106598;106599	chr2:178530243;178530242;178530241	chr2:179394970;179394969;179394968
N2AB	33817	101674;101675;101676	chr2:178530243;178530242;178530241	chr2:179394970;179394969;179394968
N2A	32890	98893;98894;98895	chr2:178530243;178530242;178530241	chr2:179394970;179394969;179394968
N2B	26393	79402;79403;79404	chr2:178530243;178530242;178530241	chr2:179394970;179394969;179394968
Novex-1	26518	79777;79778;79779	chr2:178530243;178530242;178530241	chr2:179394970;179394969;179394968
Novex-2	26585	79978;79979;79980	chr2:178530243;178530242;178530241	chr2:179394970;179394969;179394968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-166
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.3542
• 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	None	None	0.316	N	0.328	0.188	0.265010934533	gnomAD-4.0.0	1.38739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81371E-06	0	0
K/R	rs1558983295	None	0.972	N	0.475	0.199	0.288352970974	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.77E-05	0	0
K/T	None	None	0.986	N	0.493	0.416	0.432936702747	gnomAD-4.0.0	1.6442E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93491E-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
K/A	0.3365	likely_benign	0.3212	benign	0.061	Stabilizing	0.979	D	0.511	neutral	None	None	None	None	N
K/C	0.7905	likely_pathogenic	0.7756	pathogenic	-0.163	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/D	0.4908	ambiguous	0.4828	ambiguous	-0.04	Destabilizing	0.958	D	0.511	neutral	None	None	None	None	N
K/E	0.1373	likely_benign	0.1297	benign	-0.05	Destabilizing	0.316	N	0.328	neutral	N	0.440186668	None	None	N
K/F	0.6772	likely_pathogenic	0.6576	pathogenic	-0.233	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/G	0.4856	ambiguous	0.4879	ambiguous	-0.107	Destabilizing	0.989	D	0.474	neutral	None	None	None	None	N
K/H	0.3343	likely_benign	0.3272	benign	-0.359	Destabilizing	1.0	D	0.518	neutral	None	None	None	None	N
K/I	0.2527	likely_benign	0.2312	benign	0.417	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
K/L	0.3069	likely_benign	0.2957	benign	0.417	Stabilizing	0.989	D	0.481	neutral	None	None	None	None	N
K/M	0.2033	likely_benign	0.1911	benign	0.227	Stabilizing	1.0	D	0.526	neutral	N	0.505451655	None	None	N
K/N	0.2877	likely_benign	0.2803	benign	0.269	Stabilizing	0.996	D	0.461	neutral	N	0.500544481	None	None	N
K/P	0.8884	likely_pathogenic	0.9069	pathogenic	0.325	Stabilizing	0.999	D	0.537	neutral	None	None	None	None	N
K/Q	0.1364	likely_benign	0.1299	benign	0.081	Stabilizing	0.972	D	0.472	neutral	N	0.462639454	None	None	N
K/R	0.1012	likely_benign	0.1006	benign	0.022	Stabilizing	0.972	D	0.475	neutral	N	0.46841342	None	None	N
K/S	0.3772	ambiguous	0.3671	ambiguous	-0.171	Destabilizing	0.979	D	0.481	neutral	None	None	None	None	N
K/T	0.1838	likely_benign	0.177	benign	-0.046	Destabilizing	0.986	D	0.493	neutral	N	0.491751639	None	None	N
K/V	0.2714	likely_benign	0.2521	benign	0.325	Stabilizing	0.997	D	0.482	neutral	None	None	None	None	N
K/W	0.8044	likely_pathogenic	0.8009	pathogenic	-0.282	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/Y	0.5887	likely_pathogenic	0.5687	pathogenic	0.084	Stabilizing	0.999	D	0.591	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.