TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18822	56689;56690;56691	chr2:178599329;178599328;178599327	chr2:179464056;179464055;179464054
N2AB	17181	51766;51767;51768	chr2:178599329;178599328;178599327	chr2:179464056;179464055;179464054
N2A	16254	48985;48986;48987	chr2:178599329;178599328;178599327	chr2:179464056;179464055;179464054
N2B	9757	29494;29495;29496	chr2:178599329;178599328;178599327	chr2:179464056;179464055;179464054
Novex-1	9882	29869;29870;29871	chr2:178599329;178599328;178599327	chr2:179464056;179464055;179464054
Novex-2	9949	30070;30071;30072	chr2:178599329;178599328;178599327	chr2:179464056;179464055;179464054
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-24
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0539
• 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
I/T	rs771542159	-3.427	0.001	N	0.624	0.387	0.612226609336	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
I/T	rs771542159	-3.427	0.001	N	0.624	0.387	0.612226609336	gnomAD-4.0.0	5.48643E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.40289E-06	0	3.32049E-05
I/V	None	None	None	N	0.155	0.055	0.356484672536	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.8377	likely_pathogenic	0.8414	pathogenic	-3.089	Highly Destabilizing	0.116	N	0.637	neutral	None	None	None	None	N
I/C	0.9572	likely_pathogenic	0.9497	pathogenic	-2.36	Highly Destabilizing	0.944	D	0.794	deleterious	None	None	None	None	N
I/D	0.9989	likely_pathogenic	0.9986	pathogenic	-3.662	Highly Destabilizing	0.69	D	0.824	deleterious	None	None	None	None	N
I/E	0.9954	likely_pathogenic	0.9948	pathogenic	-3.353	Highly Destabilizing	0.69	D	0.819	deleterious	None	None	None	None	N
I/F	0.6465	likely_pathogenic	0.6154	pathogenic	-1.798	Destabilizing	0.627	D	0.599	neutral	D	0.522467043	None	None	N
I/G	0.9893	likely_pathogenic	0.989	pathogenic	-3.649	Highly Destabilizing	0.388	N	0.813	deleterious	None	None	None	None	N
I/H	0.9962	likely_pathogenic	0.995	pathogenic	-3.242	Highly Destabilizing	0.981	D	0.876	deleterious	None	None	None	None	N
I/K	0.9912	likely_pathogenic	0.9892	pathogenic	-2.457	Highly Destabilizing	0.69	D	0.817	deleterious	None	None	None	None	N
I/L	0.1953	likely_benign	0.1905	benign	-1.373	Destabilizing	0.041	N	0.324	neutral	N	0.450509945	None	None	N
I/M	0.2661	likely_benign	0.2522	benign	-1.693	Destabilizing	0.627	D	0.571	neutral	N	0.484359202	None	None	N
I/N	0.9904	likely_pathogenic	0.9872	pathogenic	-3.174	Highly Destabilizing	0.627	D	0.856	deleterious	D	0.522720533	None	None	N
I/P	0.9924	likely_pathogenic	0.9928	pathogenic	-1.942	Destabilizing	0.818	D	0.849	deleterious	None	None	None	None	N
I/Q	0.9922	likely_pathogenic	0.9904	pathogenic	-2.819	Highly Destabilizing	0.818	D	0.87	deleterious	None	None	None	None	N
I/R	0.9856	likely_pathogenic	0.9825	pathogenic	-2.469	Highly Destabilizing	0.69	D	0.863	deleterious	None	None	None	None	N
I/S	0.9696	likely_pathogenic	0.9652	pathogenic	-3.652	Highly Destabilizing	0.193	N	0.752	deleterious	D	0.522720533	None	None	N
I/T	0.7939	likely_pathogenic	0.7894	pathogenic	-3.193	Highly Destabilizing	0.001	N	0.624	neutral	N	0.511110738	None	None	N
I/V	0.0941	likely_benign	0.0998	benign	-1.942	Destabilizing	None	N	0.155	neutral	N	0.402072919	None	None	N
I/W	0.9892	likely_pathogenic	0.9862	pathogenic	-2.109	Highly Destabilizing	0.981	D	0.859	deleterious	None	None	None	None	N
I/Y	0.9759	likely_pathogenic	0.9706	pathogenic	-2.066	Highly Destabilizing	0.818	D	0.763	deleterious	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.