TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18767	56524;56525;56526	chr2:178599602;178599601;178599600	chr2:179464329;179464328;179464327
N2AB	17126	51601;51602;51603	chr2:178599602;178599601;178599600	chr2:179464329;179464328;179464327
N2A	16199	48820;48821;48822	chr2:178599602;178599601;178599600	chr2:179464329;179464328;179464327
N2B	9702	29329;29330;29331	chr2:178599602;178599601;178599600	chr2:179464329;179464328;179464327
Novex-1	9827	29704;29705;29706	chr2:178599602;178599601;178599600	chr2:179464329;179464328;179464327
Novex-2	9894	29905;29906;29907	chr2:178599602;178599601;178599600	chr2:179464329;179464328;179464327
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-116
• Domain position: 80
• Structural Position: 159
• Q(SASA): 0.3557
• 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
V/I	rs1275550493	-0.287	0.081	N	0.334	0.09	0.528409864224	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	6.51042E-04	None	0	None	0	0	0
V/I	rs1275550493	-0.287	0.081	N	0.334	0.09	0.528409864224	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93949E-04	None	0	0	0	0	0
V/I	rs1275550493	-0.287	0.081	N	0.334	0.09	0.528409864224	gnomAD-4.0.0	2.03024E-06	None	None	None	None	I	None	0	0	None	0	1.13817E-04	None	0	0	1.20501E-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
V/A	0.1203	likely_benign	0.1189	benign	-0.823	Destabilizing	None	N	0.125	neutral	N	0.460772584	None	None	I
V/C	0.5996	likely_pathogenic	0.6367	pathogenic	-0.674	Destabilizing	0.883	D	0.501	neutral	None	None	None	None	I
V/D	0.2987	likely_benign	0.2781	benign	-0.686	Destabilizing	0.124	N	0.581	neutral	None	None	None	None	I
V/E	0.1522	likely_benign	0.1473	benign	-0.8	Destabilizing	None	N	0.275	neutral	N	0.443936263	None	None	I
V/F	0.1735	likely_benign	0.1754	benign	-1.111	Destabilizing	0.667	D	0.511	neutral	None	None	None	None	I
V/G	0.2042	likely_benign	0.1949	benign	-0.977	Destabilizing	0.042	N	0.596	neutral	N	0.49332772	None	None	I
V/H	0.3869	ambiguous	0.4197	ambiguous	-0.604	Destabilizing	0.667	D	0.578	neutral	None	None	None	None	I
V/I	0.0722	likely_benign	0.0742	benign	-0.557	Destabilizing	0.081	N	0.334	neutral	N	0.462159451	None	None	I
V/K	0.171	likely_benign	0.1733	benign	-0.557	Destabilizing	0.124	N	0.552	neutral	None	None	None	None	I
V/L	0.1654	likely_benign	0.1801	benign	-0.557	Destabilizing	0.042	N	0.355	neutral	N	0.521743685	None	None	I
V/M	0.103	likely_benign	0.1078	benign	-0.335	Destabilizing	0.859	D	0.461	neutral	None	None	None	None	I
V/N	0.1914	likely_benign	0.1945	benign	-0.284	Destabilizing	0.22	N	0.614	neutral	None	None	None	None	I
V/P	0.9507	likely_pathogenic	0.9201	pathogenic	-0.611	Destabilizing	0.364	N	0.572	neutral	None	None	None	None	I
V/Q	0.1637	likely_benign	0.17	benign	-0.604	Destabilizing	0.124	N	0.571	neutral	None	None	None	None	I
V/R	0.1971	likely_benign	0.2027	benign	-0.004	Destabilizing	0.22	N	0.595	neutral	None	None	None	None	I
V/S	0.1301	likely_benign	0.1325	benign	-0.662	Destabilizing	0.005	N	0.275	neutral	None	None	None	None	I
V/T	0.0984	likely_benign	0.0967	benign	-0.683	Destabilizing	0.004	N	0.133	neutral	None	None	None	None	I
V/W	0.7811	likely_pathogenic	0.7895	pathogenic	-1.169	Destabilizing	0.958	D	0.611	neutral	None	None	None	None	I
V/Y	0.4818	ambiguous	0.5069	ambiguous	-0.851	Destabilizing	0.859	D	0.511	neutral	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.