TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14269	43030;43031;43032	chr2:178633554;178633553;178633552	chr2:179498281;179498280;179498279
N2AB	12628	38107;38108;38109	chr2:178633554;178633553;178633552	chr2:179498281;179498280;179498279
N2A	11701	35326;35327;35328	chr2:178633554;178633553;178633552	chr2:179498281;179498280;179498279
N2B	5204	15835;15836;15837	chr2:178633554;178633553;178633552	chr2:179498281;179498280;179498279
Novex-1	5329	16210;16211;16212	chr2:178633554;178633553;178633552	chr2:179498281;179498280;179498279
Novex-2	5396	16411;16412;16413	chr2:178633554;178633553;178633552	chr2:179498281;179498280;179498279
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-93
• Domain position: 39
• Structural Position: 58
• Q(SASA): 0.1304
• 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
I/M	rs778681091	None	0.331	D	0.665	0.188	0.1749357433	gnomAD-4.0.0	1.59212E-06	None	None	None	None	N	None	0	0	None	0	2.78118E-05	None	0	0	0	0	0
I/V	rs941635511	None	0.025	N	0.406	0.106	0.351180957027	gnomAD-4.0.0	4.7906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.11575E-05	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
I/A	0.6185	likely_pathogenic	0.4217	ambiguous	-2.315	Highly Destabilizing	0.272	N	0.628	neutral	None	None	None	None	N
I/C	0.9125	likely_pathogenic	0.832	pathogenic	-1.471	Destabilizing	0.968	D	0.722	prob.delet.	None	None	None	None	N
I/D	0.9859	likely_pathogenic	0.9621	pathogenic	-3.139	Highly Destabilizing	0.89	D	0.821	deleterious	None	None	None	None	N
I/E	0.9601	likely_pathogenic	0.9035	pathogenic	-2.869	Highly Destabilizing	0.726	D	0.815	deleterious	None	None	None	None	N
I/F	0.3861	ambiguous	0.2478	benign	-1.542	Destabilizing	0.331	N	0.636	neutral	D	0.695413167	None	None	N
I/G	0.9474	likely_pathogenic	0.8818	pathogenic	-2.833	Highly Destabilizing	0.726	D	0.813	deleterious	None	None	None	None	N
I/H	0.9544	likely_pathogenic	0.8755	pathogenic	-2.444	Highly Destabilizing	0.968	D	0.799	deleterious	None	None	None	None	N
I/K	0.9297	likely_pathogenic	0.8286	pathogenic	-1.879	Destabilizing	0.726	D	0.809	deleterious	None	None	None	None	N
I/L	0.1054	likely_benign	0.0757	benign	-0.781	Destabilizing	None	N	0.205	neutral	N	0.460642768	None	None	N
I/M	0.1441	likely_benign	0.1012	benign	-0.717	Destabilizing	0.331	N	0.665	neutral	D	0.609624819	None	None	N
I/N	0.8839	likely_pathogenic	0.7483	pathogenic	-2.453	Highly Destabilizing	0.859	D	0.825	deleterious	D	0.734236651	None	None	N
I/P	0.9749	likely_pathogenic	0.9439	pathogenic	-1.281	Destabilizing	0.89	D	0.825	deleterious	None	None	None	None	N
I/Q	0.9349	likely_pathogenic	0.8432	pathogenic	-2.226	Highly Destabilizing	0.89	D	0.821	deleterious	None	None	None	None	N
I/R	0.8923	likely_pathogenic	0.7481	pathogenic	-1.82	Destabilizing	0.726	D	0.823	deleterious	None	None	None	None	N
I/S	0.8578	likely_pathogenic	0.6864	pathogenic	-2.976	Highly Destabilizing	0.667	D	0.745	deleterious	D	0.711154155	None	None	N
I/T	0.5458	ambiguous	0.3012	benign	-2.558	Highly Destabilizing	0.22	N	0.677	prob.neutral	D	0.728365637	None	None	N
I/V	0.1208	likely_benign	0.0972	benign	-1.281	Destabilizing	0.025	N	0.406	neutral	N	0.51270774	None	None	N
I/W	0.9561	likely_pathogenic	0.8905	pathogenic	-1.958	Destabilizing	0.968	D	0.786	deleterious	None	None	None	None	N
I/Y	0.8511	likely_pathogenic	0.7229	pathogenic	-1.619	Destabilizing	0.726	D	0.766	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.