TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28475	85648;85649;85650	chr2:178560709;178560708;178560707	chr2:179425436;179425435;179425434
N2AB	26834	80725;80726;80727	chr2:178560709;178560708;178560707	chr2:179425436;179425435;179425434
N2A	25907	77944;77945;77946	chr2:178560709;178560708;178560707	chr2:179425436;179425435;179425434
N2B	19410	58453;58454;58455	chr2:178560709;178560708;178560707	chr2:179425436;179425435;179425434
Novex-1	19535	58828;58829;58830	chr2:178560709;178560708;178560707	chr2:179425436;179425435;179425434
Novex-2	19602	59029;59030;59031	chr2:178560709;178560708;178560707	chr2:179425436;179425435;179425434
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-95
• Domain position: 26
• Structural Position: 27
• Q(SASA): 0.1632
• 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
P/L	None	None	0.978	D	0.881	0.562	0.891450760401	gnomAD-4.0.0	2.73718E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59787E-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
P/A	0.6787	likely_pathogenic	0.6641	pathogenic	-1.861	Destabilizing	0.865	D	0.685	prob.neutral	D	0.60968895	None	None	N
P/C	0.9401	likely_pathogenic	0.924	pathogenic	-1.213	Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
P/D	0.9927	likely_pathogenic	0.9927	pathogenic	-1.906	Destabilizing	0.983	D	0.831	deleterious	None	None	None	None	N
P/E	0.9772	likely_pathogenic	0.978	pathogenic	-1.866	Destabilizing	0.983	D	0.828	deleterious	None	None	None	None	N
P/F	0.9923	likely_pathogenic	0.9907	pathogenic	-1.364	Destabilizing	0.998	D	0.904	deleterious	None	None	None	None	N
P/G	0.9633	likely_pathogenic	0.9568	pathogenic	-2.239	Highly Destabilizing	0.895	D	0.799	deleterious	None	None	None	None	N
P/H	0.9601	likely_pathogenic	0.9575	pathogenic	-1.841	Destabilizing	0.997	D	0.897	deleterious	D	0.651851835	None	None	N
P/I	0.9104	likely_pathogenic	0.9061	pathogenic	-0.889	Destabilizing	0.992	D	0.889	deleterious	None	None	None	None	N
P/K	0.9813	likely_pathogenic	0.9832	pathogenic	-1.664	Destabilizing	0.968	D	0.831	deleterious	None	None	None	None	N
P/L	0.7363	likely_pathogenic	0.734	pathogenic	-0.889	Destabilizing	0.978	D	0.881	deleterious	D	0.650842814	None	None	N
P/M	0.9554	likely_pathogenic	0.9461	pathogenic	-0.628	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
P/N	0.9849	likely_pathogenic	0.9845	pathogenic	-1.452	Destabilizing	0.968	D	0.903	deleterious	None	None	None	None	N
P/Q	0.9406	likely_pathogenic	0.9369	pathogenic	-1.576	Destabilizing	0.983	D	0.857	deleterious	None	None	None	None	N
P/R	0.9404	likely_pathogenic	0.9464	pathogenic	-1.148	Destabilizing	0.978	D	0.887	deleterious	D	0.63563067	None	None	N
P/S	0.8914	likely_pathogenic	0.8763	pathogenic	-1.981	Destabilizing	0.284	N	0.563	neutral	D	0.58026476	None	None	N
P/T	0.8358	likely_pathogenic	0.8192	pathogenic	-1.827	Destabilizing	0.957	D	0.805	deleterious	D	0.635428866	None	None	N
P/V	0.8228	likely_pathogenic	0.8145	pathogenic	-1.18	Destabilizing	0.983	D	0.883	deleterious	None	None	None	None	N
P/W	0.9959	likely_pathogenic	0.9951	pathogenic	-1.621	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
P/Y	0.9901	likely_pathogenic	0.9898	pathogenic	-1.357	Destabilizing	0.999	D	0.903	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.