TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17578	52957;52958;52959	chr2:178608055;178608054;178608053	chr2:179472782;179472781;179472780
N2AB	15937	48034;48035;48036	chr2:178608055;178608054;178608053	chr2:179472782;179472781;179472780
N2A	15010	45253;45254;45255	chr2:178608055;178608054;178608053	chr2:179472782;179472781;179472780
N2B	8513	25762;25763;25764	chr2:178608055;178608054;178608053	chr2:179472782;179472781;179472780
Novex-1	8638	26137;26138;26139	chr2:178608055;178608054;178608053	chr2:179472782;179472781;179472780
Novex-2	8705	26338;26339;26340	chr2:178608055;178608054;178608053	chr2:179472782;179472781;179472780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-16
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.31
• 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/A	rs764884631	-1.468	0.892	N	0.495	0.286	0.49376247819	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.68E-05	None	0	None	0	0	0
V/A	rs764884631	-1.468	0.892	N	0.495	0.286	0.49376247819	gnomAD-4.0.0	1.59401E-06	None	None	None	None	N	None	0	0	None	0	2.7947E-05	None	0	0	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
V/A	0.67	likely_pathogenic	0.6111	pathogenic	-1.388	Destabilizing	0.892	D	0.495	neutral	N	0.50187734	None	None	N
V/C	0.9028	likely_pathogenic	0.8658	pathogenic	-0.994	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
V/D	0.9585	likely_pathogenic	0.9286	pathogenic	-1.126	Destabilizing	0.994	D	0.843	deleterious	N	0.52103133	None	None	N
V/E	0.89	likely_pathogenic	0.8354	pathogenic	-1.107	Destabilizing	0.996	D	0.818	deleterious	None	None	None	None	N
V/F	0.598	likely_pathogenic	0.4482	ambiguous	-0.986	Destabilizing	0.967	D	0.756	deleterious	N	0.47523358	None	None	N
V/G	0.7954	likely_pathogenic	0.7267	pathogenic	-1.726	Destabilizing	0.983	D	0.829	deleterious	N	0.493519326	None	None	N
V/H	0.9699	likely_pathogenic	0.9392	pathogenic	-1.194	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
V/I	0.0857	likely_benign	0.0767	benign	-0.559	Destabilizing	0.011	N	0.189	neutral	N	0.456203766	None	None	N
V/K	0.9143	likely_pathogenic	0.8506	pathogenic	-1.238	Destabilizing	0.987	D	0.821	deleterious	None	None	None	None	N
V/L	0.5332	ambiguous	0.3931	ambiguous	-0.559	Destabilizing	0.369	N	0.353	neutral	N	0.500551976	None	None	N
V/M	0.4785	ambiguous	0.3568	ambiguous	-0.49	Destabilizing	0.975	D	0.617	neutral	None	None	None	None	N
V/N	0.9133	likely_pathogenic	0.8479	pathogenic	-1.054	Destabilizing	0.996	D	0.839	deleterious	None	None	None	None	N
V/P	0.808	likely_pathogenic	0.7561	pathogenic	-0.8	Destabilizing	0.996	D	0.82	deleterious	None	None	None	None	N
V/Q	0.9088	likely_pathogenic	0.8431	pathogenic	-1.171	Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	N
V/R	0.9052	likely_pathogenic	0.8321	pathogenic	-0.745	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
V/S	0.8709	likely_pathogenic	0.8104	pathogenic	-1.594	Destabilizing	0.987	D	0.801	deleterious	None	None	None	None	N
V/T	0.7664	likely_pathogenic	0.6923	pathogenic	-1.453	Destabilizing	0.916	D	0.597	neutral	None	None	None	None	N
V/W	0.9748	likely_pathogenic	0.9491	pathogenic	-1.18	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
V/Y	0.9194	likely_pathogenic	0.8589	pathogenic	-0.886	Destabilizing	0.987	D	0.761	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.