TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7470	22633;22634;22635	chr2:178722379;178722378;178722377	chr2:179587106;179587105;179587104
N2AB	7153	21682;21683;21684	chr2:178722379;178722378;178722377	chr2:179587106;179587105;179587104
N2A	6226	18901;18902;18903	chr2:178722379;178722378;178722377	chr2:179587106;179587105;179587104
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-59
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4938
• 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/A	rs1429215263	-0.381	0.425	N	0.219	0.14	0.568500581595	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
V/A	rs1429215263	-0.381	0.425	N	0.219	0.14	0.568500581595	gnomAD-4.0.0	1.36874E-06	None	None	None	None	I	None	0	0	None	0	2.52118E-05	None	0	0	8.99619E-07	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	0.1285	likely_benign	0.1778	benign	-0.507	Destabilizing	0.425	N	0.219	neutral	N	0.487785827	None	None	I
V/C	0.7646	likely_pathogenic	0.8371	pathogenic	-0.717	Destabilizing	0.995	D	0.305	neutral	None	None	None	None	I
V/D	0.2269	likely_benign	0.3284	benign	-0.034	Destabilizing	0.003	N	0.197	neutral	None	None	None	None	I
V/E	0.1875	likely_benign	0.2515	benign	-0.127	Destabilizing	0.27	N	0.283	neutral	N	0.437220934	None	None	I
V/F	0.1423	likely_benign	0.1742	benign	-0.601	Destabilizing	0.893	D	0.322	neutral	None	None	None	None	I
V/G	0.1998	likely_benign	0.2655	benign	-0.651	Destabilizing	0.642	D	0.353	neutral	N	0.492154284	None	None	I
V/H	0.3843	ambiguous	0.5164	ambiguous	-0.11	Destabilizing	0.981	D	0.359	neutral	None	None	None	None	I
V/I	0.0697	likely_benign	0.0773	benign	-0.272	Destabilizing	0.006	N	0.157	neutral	N	0.449768944	None	None	I
V/K	0.271	likely_benign	0.362	ambiguous	-0.409	Destabilizing	0.031	N	0.211	neutral	None	None	None	None	I
V/L	0.1309	likely_benign	0.1632	benign	-0.272	Destabilizing	0.27	N	0.243	neutral	N	0.465314399	None	None	I
V/M	0.1179	likely_benign	0.1452	benign	-0.424	Destabilizing	0.893	D	0.281	neutral	None	None	None	None	I
V/N	0.2066	likely_benign	0.3247	benign	-0.234	Destabilizing	0.704	D	0.372	neutral	None	None	None	None	I
V/P	0.715	likely_pathogenic	0.7946	pathogenic	-0.315	Destabilizing	0.981	D	0.405	neutral	None	None	None	None	I
V/Q	0.2217	likely_benign	0.2945	benign	-0.424	Destabilizing	0.893	D	0.403	neutral	None	None	None	None	I
V/R	0.219	likely_benign	0.2842	benign	0.074	Stabilizing	0.007	N	0.259	neutral	None	None	None	None	I
V/S	0.1457	likely_benign	0.2123	benign	-0.653	Destabilizing	0.704	D	0.323	neutral	None	None	None	None	I
V/T	0.1194	likely_benign	0.1664	benign	-0.638	Destabilizing	0.704	D	0.154	neutral	None	None	None	None	I
V/W	0.6703	likely_pathogenic	0.7344	pathogenic	-0.674	Destabilizing	0.995	D	0.417	neutral	None	None	None	None	I
V/Y	0.4568	ambiguous	0.5634	ambiguous	-0.388	Destabilizing	0.981	D	0.317	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.