TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26614	80065;80066;80067	chr2:178566292;178566291;178566290	chr2:179431019;179431018;179431017
N2AB	24973	75142;75143;75144	chr2:178566292;178566291;178566290	chr2:179431019;179431018;179431017
N2A	24046	72361;72362;72363	chr2:178566292;178566291;178566290	chr2:179431019;179431018;179431017
N2B	17549	52870;52871;52872	chr2:178566292;178566291;178566290	chr2:179431019;179431018;179431017
Novex-1	17674	53245;53246;53247	chr2:178566292;178566291;178566290	chr2:179431019;179431018;179431017
Novex-2	17741	53446;53447;53448	chr2:178566292;178566291;178566290	chr2:179431019;179431018;179431017
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: Ig-138
• Domain position: 21
• Structural Position: 33
• Q(SASA): 0.1068
• 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/M	None	None	0.994	N	0.708	0.248	0.304435445954	gnomAD-4.0.0	1.59147E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	None	0	0	0	0	0
I/V	rs998950249	None	0.426	N	0.479	0.163	0.335414705075	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs998950249	None	0.426	N	0.479	0.163	0.335414705075	gnomAD-4.0.0	1.85923E-06	None	None	None	None	N	None	2.67001E-05	0	None	0	0	None	0	1.6442E-04	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
I/A	0.9401	likely_pathogenic	0.9349	pathogenic	-2.647	Highly Destabilizing	0.033	N	0.569	neutral	None	None	None	None	N
I/C	0.93	likely_pathogenic	0.9291	pathogenic	-1.819	Destabilizing	0.997	D	0.778	deleterious	None	None	None	None	N
I/D	0.9985	likely_pathogenic	0.9984	pathogenic	-3.141	Highly Destabilizing	0.987	D	0.876	deleterious	None	None	None	None	N
I/E	0.997	likely_pathogenic	0.9965	pathogenic	-2.912	Highly Destabilizing	0.975	D	0.872	deleterious	None	None	None	None	N
I/F	0.6363	likely_pathogenic	0.5859	pathogenic	-1.69	Destabilizing	0.983	D	0.748	deleterious	N	0.456933108	None	None	N
I/G	0.9927	likely_pathogenic	0.9917	pathogenic	-3.149	Highly Destabilizing	0.95	D	0.846	deleterious	None	None	None	None	N
I/H	0.9908	likely_pathogenic	0.9892	pathogenic	-2.413	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
I/K	0.9917	likely_pathogenic	0.9908	pathogenic	-2.247	Highly Destabilizing	0.975	D	0.87	deleterious	None	None	None	None	N
I/L	0.3171	likely_benign	0.2945	benign	-1.184	Destabilizing	0.63	D	0.523	neutral	N	0.509272168	None	None	N
I/M	0.4351	ambiguous	0.4187	ambiguous	-1.006	Destabilizing	0.994	D	0.708	prob.delet.	N	0.5052905	None	None	N
I/N	0.9729	likely_pathogenic	0.971	pathogenic	-2.633	Highly Destabilizing	0.983	D	0.869	deleterious	N	0.475544342	None	None	N
I/P	0.9948	likely_pathogenic	0.9947	pathogenic	-1.656	Destabilizing	0.987	D	0.873	deleterious	None	None	None	None	N
I/Q	0.9912	likely_pathogenic	0.9896	pathogenic	-2.524	Highly Destabilizing	0.987	D	0.872	deleterious	None	None	None	None	N
I/R	0.9867	likely_pathogenic	0.9847	pathogenic	-1.899	Destabilizing	0.987	D	0.869	deleterious	None	None	None	None	N
I/S	0.9532	likely_pathogenic	0.9489	pathogenic	-3.247	Highly Destabilizing	0.805	D	0.829	deleterious	N	0.452324753	None	None	N
I/T	0.9364	likely_pathogenic	0.9284	pathogenic	-2.874	Highly Destabilizing	0.892	D	0.787	deleterious	N	0.463174079	None	None	N
I/V	0.1227	likely_benign	0.1243	benign	-1.656	Destabilizing	0.426	N	0.479	neutral	N	0.369933497	None	None	N
I/W	0.9923	likely_pathogenic	0.9917	pathogenic	-2.004	Highly Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
I/Y	0.9618	likely_pathogenic	0.9574	pathogenic	-1.733	Destabilizing	0.996	D	0.776	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.