TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26174	78745;78746;78747	chr2:178567612;178567611;178567610	chr2:179432339;179432338;179432337
N2AB	24533	73822;73823;73824	chr2:178567612;178567611;178567610	chr2:179432339;179432338;179432337
N2A	23606	71041;71042;71043	chr2:178567612;178567611;178567610	chr2:179432339;179432338;179432337
N2B	17109	51550;51551;51552	chr2:178567612;178567611;178567610	chr2:179432339;179432338;179432337
Novex-1	17234	51925;51926;51927	chr2:178567612;178567611;178567610	chr2:179432339;179432338;179432337
Novex-2	17301	52126;52127;52128	chr2:178567612;178567611;178567610	chr2:179432339;179432338;179432337
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: Fn3-78
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.8028
• Predicted PPI site: I

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	rs1157744481	None	0.046	N	0.368	0.205	0.171388866994	gnomAD-4.0.0	3.19164E-06	None	None	None	None	I	None	5.66829E-05	0	None	0	2.78118E-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
K/A	0.2314	likely_benign	0.2201	benign	-0.105	Destabilizing	0.953	D	0.661	neutral	None	None	None	None	I
K/C	0.6198	likely_pathogenic	0.5801	pathogenic	-0.273	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
K/D	0.4533	ambiguous	0.4349	ambiguous	0.152	Stabilizing	0.91	D	0.672	neutral	None	None	None	None	I
K/E	0.139	likely_benign	0.1319	benign	0.185	Stabilizing	0.046	N	0.368	neutral	N	0.388378476	None	None	I
K/F	0.6417	likely_pathogenic	0.5862	pathogenic	-0.189	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/G	0.3859	ambiguous	0.3668	ambiguous	-0.346	Destabilizing	0.976	D	0.632	neutral	None	None	None	None	I
K/H	0.3052	likely_benign	0.2881	benign	-0.615	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	I
K/I	0.2415	likely_benign	0.217	benign	0.46	Stabilizing	0.991	D	0.71	prob.delet.	N	0.490198909	None	None	I
K/L	0.2298	likely_benign	0.2049	benign	0.46	Stabilizing	0.986	D	0.62	neutral	None	None	None	None	I
K/M	0.188	likely_benign	0.1694	benign	0.203	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	I
K/N	0.3293	likely_benign	0.311	benign	0.102	Stabilizing	0.982	D	0.663	neutral	N	0.477547303	None	None	I
K/P	0.3503	ambiguous	0.3545	ambiguous	0.301	Stabilizing	0.993	D	0.691	prob.neutral	None	None	None	None	I
K/Q	0.1158	likely_benign	0.113	benign	-0.027	Destabilizing	0.964	D	0.667	neutral	N	0.493660502	None	None	I
K/R	0.0887	likely_benign	0.086	benign	-0.14	Destabilizing	0.1	N	0.355	neutral	N	0.457297057	None	None	I
K/S	0.3184	likely_benign	0.298	benign	-0.43	Destabilizing	0.953	D	0.653	neutral	None	None	None	None	I
K/T	0.1586	likely_benign	0.1523	benign	-0.23	Destabilizing	0.982	D	0.653	neutral	N	0.489332118	None	None	I
K/V	0.2144	likely_benign	0.1958	benign	0.301	Stabilizing	0.993	D	0.655	neutral	None	None	None	None	I
K/W	0.7547	likely_pathogenic	0.7047	pathogenic	-0.176	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
K/Y	0.5369	ambiguous	0.4902	ambiguous	0.161	Stabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I

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.