TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16092	48499;48500;48501	chr2:178616517;178616516;178616515	chr2:179481244;179481243;179481242
N2AB	14451	43576;43577;43578	chr2:178616517;178616516;178616515	chr2:179481244;179481243;179481242
N2A	13524	40795;40796;40797	chr2:178616517;178616516;178616515	chr2:179481244;179481243;179481242
N2B	7027	21304;21305;21306	chr2:178616517;178616516;178616515	chr2:179481244;179481243;179481242
Novex-1	7152	21679;21680;21681	chr2:178616517;178616516;178616515	chr2:179481244;179481243;179481242
Novex-2	7219	21880;21881;21882	chr2:178616517;178616516;178616515	chr2:179481244;179481243;179481242
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-4
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.077
• 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	None	None	0.001	N	0.215	0.038	0.199424873507	gnomAD-4.0.0	3.18841E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72912E-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	0.7356	likely_pathogenic	0.7223	pathogenic	-2.686	Highly Destabilizing	0.334	N	0.607	neutral	D	0.70542067	None	None	N
V/C	0.9363	likely_pathogenic	0.9362	pathogenic	-2.141	Highly Destabilizing	0.982	D	0.759	deleterious	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.9939	pathogenic	-3.655	Highly Destabilizing	0.781	D	0.904	deleterious	D	0.765805413	None	None	N
V/E	0.9881	likely_pathogenic	0.9817	pathogenic	-3.326	Highly Destabilizing	0.826	D	0.881	deleterious	None	None	None	None	N
V/F	0.7311	likely_pathogenic	0.6562	pathogenic	-1.585	Destabilizing	0.638	D	0.779	deleterious	D	0.728751676	None	None	N
V/G	0.9189	likely_pathogenic	0.9007	pathogenic	-3.285	Highly Destabilizing	0.781	D	0.895	deleterious	D	0.765805413	None	None	N
V/H	0.9962	likely_pathogenic	0.9942	pathogenic	-3.13	Highly Destabilizing	0.982	D	0.867	deleterious	None	None	None	None	N
V/I	0.0693	likely_benign	0.0654	benign	-0.913	Destabilizing	0.001	N	0.215	neutral	N	0.460634674	None	None	N
V/K	0.9907	likely_pathogenic	0.9855	pathogenic	-2.286	Highly Destabilizing	0.826	D	0.882	deleterious	None	None	None	None	N
V/L	0.2713	likely_benign	0.2767	benign	-0.913	Destabilizing	0.034	N	0.465	neutral	N	0.500209573	None	None	N
V/M	0.4571	ambiguous	0.4384	ambiguous	-1.226	Destabilizing	0.7	D	0.673	neutral	None	None	None	None	N
V/N	0.9901	likely_pathogenic	0.9832	pathogenic	-3.046	Highly Destabilizing	0.935	D	0.905	deleterious	None	None	None	None	N
V/P	0.9824	likely_pathogenic	0.9678	pathogenic	-1.491	Destabilizing	0.935	D	0.89	deleterious	None	None	None	None	N
V/Q	0.9866	likely_pathogenic	0.9811	pathogenic	-2.659	Highly Destabilizing	0.935	D	0.901	deleterious	None	None	None	None	N
V/R	0.9822	likely_pathogenic	0.9729	pathogenic	-2.375	Highly Destabilizing	0.826	D	0.906	deleterious	None	None	None	None	N
V/S	0.9552	likely_pathogenic	0.9411	pathogenic	-3.509	Highly Destabilizing	0.826	D	0.865	deleterious	None	None	None	None	N
V/T	0.8118	likely_pathogenic	0.7911	pathogenic	-3.022	Highly Destabilizing	0.399	N	0.647	neutral	None	None	None	None	N
V/W	0.9935	likely_pathogenic	0.989	pathogenic	-2.097	Highly Destabilizing	0.982	D	0.834	deleterious	None	None	None	None	N
V/Y	0.9805	likely_pathogenic	0.9676	pathogenic	-1.877	Destabilizing	0.826	D	0.777	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.