TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23472	70639;70640;70641	chr2:178575718;178575717;178575716	chr2:179440445;179440444;179440443
N2AB	21831	65716;65717;65718	chr2:178575718;178575717;178575716	chr2:179440445;179440444;179440443
N2A	20904	62935;62936;62937	chr2:178575718;178575717;178575716	chr2:179440445;179440444;179440443
N2B	14407	43444;43445;43446	chr2:178575718;178575717;178575716	chr2:179440445;179440444;179440443
Novex-1	14532	43819;43820;43821	chr2:178575718;178575717;178575716	chr2:179440445;179440444;179440443
Novex-2	14599	44020;44021;44022	chr2:178575718;178575717;178575716	chr2:179440445;179440444;179440443
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: Fn3-58
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0972
• 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	rs556399127	-0.706	0.29	N	0.213	0.153	0.473065174198	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
V/I	rs556399127	-0.706	0.29	N	0.213	0.153	0.473065174198	gnomAD-4.0.0	3.18349E-06	None	None	None	None	N	None	0	0	None	0	2.77809E-05	None	0	0	2.8591E-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	0.8671	likely_pathogenic	0.8889	pathogenic	-2.408	Highly Destabilizing	0.987	D	0.602	neutral	D	0.552504397	None	None	N
V/C	0.9758	likely_pathogenic	0.9839	pathogenic	-1.981	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/D	0.9994	likely_pathogenic	0.9994	pathogenic	-3.421	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/E	0.9967	likely_pathogenic	0.9971	pathogenic	-3.109	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.564785755	None	None	N
V/F	0.8923	likely_pathogenic	0.9227	pathogenic	-1.275	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
V/G	0.9758	likely_pathogenic	0.9802	pathogenic	-3.016	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.564785755	None	None	N
V/H	0.9989	likely_pathogenic	0.9992	pathogenic	-2.907	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/I	0.0733	likely_benign	0.0733	benign	-0.637	Destabilizing	0.29	N	0.213	neutral	N	0.462343091	None	None	N
V/K	0.997	likely_pathogenic	0.9975	pathogenic	-1.966	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/L	0.4614	ambiguous	0.4971	ambiguous	-0.637	Destabilizing	0.853	D	0.337	neutral	N	0.485422386	None	None	N
V/M	0.6977	likely_pathogenic	0.7478	pathogenic	-0.953	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
V/N	0.9977	likely_pathogenic	0.9981	pathogenic	-2.615	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
V/P	0.9937	likely_pathogenic	0.9947	pathogenic	-1.209	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/Q	0.9959	likely_pathogenic	0.9965	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/R	0.9938	likely_pathogenic	0.9944	pathogenic	-2.031	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
V/S	0.9841	likely_pathogenic	0.9867	pathogenic	-3.143	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/T	0.8869	likely_pathogenic	0.9038	pathogenic	-2.676	Highly Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
V/W	0.9982	likely_pathogenic	0.9989	pathogenic	-1.898	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/Y	0.9941	likely_pathogenic	0.9963	pathogenic	-1.587	Destabilizing	1.0	D	0.757	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.