TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5631	17116;17117;17118	chr2:178732078;178732077;178732076	chr2:179596805;179596804;179596803
N2AB	5314	16165;16166;16167	chr2:178732078;178732077;178732076	chr2:179596805;179596804;179596803
N2A	4387	13384;13385;13386	chr2:178732078;178732077;178732076	chr2:179596805;179596804;179596803
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-39
• Domain position: 89
• Structural Position: 174
• Q(SASA): 0.1278
• 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
V/I	rs778807865	-0.338	0.002	N	0.245	0.09	0.107399877778	gnomAD-2.1.1	1.64E-05	None	None	None	None	N	None	0	2.93E-05	None	0	0	None	0	None	0	2.71E-05	0
V/I	rs778807865	-0.338	0.002	N	0.245	0.09	0.107399877778	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
V/I	rs778807865	-0.338	0.002	N	0.245	0.09	0.107399877778	gnomAD-4.0.0	1.55489E-05	None	None	None	None	N	None	0	1.70497E-05	None	0	0	None	0	0	2.42707E-05	0	2.87819E-05

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
V/A	0.4159	ambiguous	0.4604	ambiguous	-2.134	Highly Destabilizing	0.334	N	0.64	neutral	N	0.492668455	None	None	N
V/C	0.734	likely_pathogenic	0.7557	pathogenic	-1.952	Destabilizing	0.982	D	0.761	deleterious	None	None	None	None	N
V/D	0.8768	likely_pathogenic	0.9006	pathogenic	-2.417	Highly Destabilizing	0.826	D	0.839	deleterious	None	None	None	None	N
V/E	0.8119	likely_pathogenic	0.8425	pathogenic	-2.189	Highly Destabilizing	0.781	D	0.827	deleterious	N	0.504696323	None	None	N
V/F	0.1694	likely_benign	0.2014	benign	-1.286	Destabilizing	0.539	D	0.782	deleterious	None	None	None	None	N
V/G	0.5848	likely_pathogenic	0.6406	pathogenic	-2.678	Highly Destabilizing	0.781	D	0.847	deleterious	N	0.504696323	None	None	N
V/H	0.8241	likely_pathogenic	0.8582	pathogenic	-2.348	Highly Destabilizing	0.982	D	0.83	deleterious	None	None	None	None	N
V/I	0.0615	likely_benign	0.0581	benign	-0.613	Destabilizing	0.002	N	0.245	neutral	N	0.473892945	None	None	N
V/K	0.805	likely_pathogenic	0.8307	pathogenic	-1.637	Destabilizing	0.826	D	0.829	deleterious	None	None	None	None	N
V/L	0.098	likely_benign	0.0925	benign	-0.613	Destabilizing	0.002	N	0.333	neutral	N	0.380291271	None	None	N
V/M	0.1386	likely_benign	0.1455	benign	-0.893	Destabilizing	0.539	D	0.698	prob.neutral	None	None	None	None	N
V/N	0.6776	likely_pathogenic	0.6984	pathogenic	-1.981	Destabilizing	0.935	D	0.847	deleterious	None	None	None	None	N
V/P	0.8583	likely_pathogenic	0.8972	pathogenic	-1.094	Destabilizing	0.935	D	0.802	deleterious	None	None	None	None	N
V/Q	0.7368	likely_pathogenic	0.7708	pathogenic	-1.802	Destabilizing	0.935	D	0.823	deleterious	None	None	None	None	N
V/R	0.7249	likely_pathogenic	0.7529	pathogenic	-1.548	Destabilizing	0.826	D	0.842	deleterious	None	None	None	None	N
V/S	0.587	likely_pathogenic	0.6263	pathogenic	-2.683	Highly Destabilizing	0.826	D	0.828	deleterious	None	None	None	None	N
V/T	0.4493	ambiguous	0.4821	ambiguous	-2.3	Highly Destabilizing	0.399	N	0.683	prob.neutral	None	None	None	None	N
V/W	0.8028	likely_pathogenic	0.8488	pathogenic	-1.698	Destabilizing	0.982	D	0.817	deleterious	None	None	None	None	N
V/Y	0.6157	likely_pathogenic	0.6836	pathogenic	-1.346	Destabilizing	0.826	D	0.751	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.