TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15929	48010;48011;48012	chr2:178617210;178617209;178617208	chr2:179481937;179481936;179481935
N2AB	14288	43087;43088;43089	chr2:178617210;178617209;178617208	chr2:179481937;179481936;179481935
N2A	13361	40306;40307;40308	chr2:178617210;178617209;178617208	chr2:179481937;179481936;179481935
N2B	6864	20815;20816;20817	chr2:178617210;178617209;178617208	chr2:179481937;179481936;179481935
Novex-1	6989	21190;21191;21192	chr2:178617210;178617209;178617208	chr2:179481937;179481936;179481935
Novex-2	7056	21391;21392;21393	chr2:178617210;178617209;178617208	chr2:179481937;179481936;179481935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-3
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3264
• 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
K/E	rs1386533299	0.144	0.062	N	0.46	0.157	0.208816687407	gnomAD-2.1.1	6.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	4.79E-05	None	0	0	0
K/E	rs1386533299	0.144	0.062	N	0.46	0.157	0.208816687407	gnomAD-4.0.0	1.22659E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.14977E-04	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
K/A	0.2659	likely_benign	0.2813	benign	-0.794	Destabilizing	0.035	N	0.462	neutral	None	None	None	None	N
K/C	0.5081	ambiguous	0.5269	ambiguous	-0.791	Destabilizing	0.935	D	0.638	neutral	None	None	None	None	N
K/D	0.4946	ambiguous	0.4845	ambiguous	-0.468	Destabilizing	0.081	N	0.523	neutral	None	None	None	None	N
K/E	0.1743	likely_benign	0.1738	benign	-0.327	Destabilizing	0.062	N	0.46	neutral	N	0.467803148	None	None	N
K/F	0.7496	likely_pathogenic	0.7635	pathogenic	-0.343	Destabilizing	0.555	D	0.647	neutral	None	None	None	None	N
K/G	0.3748	ambiguous	0.3856	ambiguous	-1.197	Destabilizing	0.081	N	0.525	neutral	None	None	None	None	N
K/H	0.2815	likely_benign	0.2866	benign	-1.541	Destabilizing	0.38	N	0.574	neutral	None	None	None	None	N
K/I	0.2945	likely_benign	0.3089	benign	0.27	Stabilizing	0.188	N	0.629	neutral	N	0.475029999	None	None	N
K/L	0.3466	ambiguous	0.356	ambiguous	0.27	Stabilizing	0.081	N	0.521	neutral	None	None	None	None	N
K/M	0.217	likely_benign	0.2284	benign	0.145	Stabilizing	0.035	N	0.389	neutral	None	None	None	None	N
K/N	0.3012	likely_benign	0.2932	benign	-0.821	Destabilizing	None	N	0.208	neutral	N	0.477671558	None	None	N
K/P	0.5783	likely_pathogenic	0.6148	pathogenic	-0.055	Destabilizing	0.555	D	0.579	neutral	None	None	None	None	N
K/Q	0.1218	likely_benign	0.1261	benign	-0.835	Destabilizing	0.317	N	0.52	neutral	N	0.482789225	None	None	N
K/R	0.0872	likely_benign	0.0864	benign	-0.87	Destabilizing	0.117	N	0.496	neutral	N	0.478344124	None	None	N
K/S	0.2604	likely_benign	0.2549	benign	-1.461	Destabilizing	0.002	N	0.117	neutral	None	None	None	None	N
K/T	0.1136	likely_benign	0.1141	benign	-1.104	Destabilizing	0.062	N	0.473	neutral	N	0.477365578	None	None	N
K/V	0.2597	likely_benign	0.2722	benign	-0.055	Destabilizing	0.081	N	0.589	neutral	None	None	None	None	N
K/W	0.7481	likely_pathogenic	0.7466	pathogenic	-0.231	Destabilizing	0.935	D	0.677	prob.neutral	None	None	None	None	N
K/Y	0.5598	ambiguous	0.5576	ambiguous	0.055	Stabilizing	0.791	D	0.645	neutral	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.