TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23311	70156;70157;70158	chr2:178576201;178576200;178576199	chr2:179440928;179440927;179440926
N2AB	21670	65233;65234;65235	chr2:178576201;178576200;178576199	chr2:179440928;179440927;179440926
N2A	20743	62452;62453;62454	chr2:178576201;178576200;178576199	chr2:179440928;179440927;179440926
N2B	14246	42961;42962;42963	chr2:178576201;178576200;178576199	chr2:179440928;179440927;179440926
Novex-1	14371	43336;43337;43338	chr2:178576201;178576200;178576199	chr2:179440928;179440927;179440926
Novex-2	14438	43537;43538;43539	chr2:178576201;178576200;178576199	chr2:179440928;179440927;179440926
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: Fn3-57
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.4271
• 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/R	rs1025638052	None	0.892	N	0.471	0.26	0.354396617058	gnomAD-4.0.0	1.59333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02828E-05

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	0.3537	ambiguous	0.3413	ambiguous	-0.97	Destabilizing	0.845	D	0.549	neutral	None	None	None	None	N
K/C	0.5845	likely_pathogenic	0.5544	ambiguous	-1.047	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
K/D	0.6458	likely_pathogenic	0.6358	pathogenic	-0.724	Destabilizing	0.975	D	0.75	deleterious	None	None	None	None	N
K/E	0.2368	likely_benign	0.2338	benign	-0.527	Destabilizing	0.892	D	0.46	neutral	N	0.385588887	None	None	N
K/F	0.7074	likely_pathogenic	0.6859	pathogenic	-0.34	Destabilizing	0.987	D	0.792	deleterious	None	None	None	None	N
K/G	0.4896	ambiguous	0.4669	ambiguous	-1.416	Destabilizing	0.975	D	0.719	prob.delet.	None	None	None	None	N
K/H	0.2946	likely_benign	0.2741	benign	-1.603	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
K/I	0.2738	likely_benign	0.2783	benign	0.236	Stabilizing	0.967	D	0.794	deleterious	N	0.516481434	None	None	N
K/L	0.3194	likely_benign	0.3147	benign	0.236	Stabilizing	0.845	D	0.663	neutral	None	None	None	None	N
K/M	0.1711	likely_benign	0.1674	benign	0.014	Stabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
K/N	0.3585	ambiguous	0.3458	ambiguous	-1.169	Destabilizing	0.967	D	0.658	neutral	N	0.497335525	None	None	N
K/P	0.6306	likely_pathogenic	0.6203	pathogenic	-0.138	Destabilizing	0.987	D	0.8	deleterious	None	None	None	None	N
K/Q	0.1469	likely_benign	0.1413	benign	-1.061	Destabilizing	0.983	D	0.666	neutral	N	0.473439945	None	None	N
K/R	0.088	likely_benign	0.0858	benign	-0.971	Destabilizing	0.892	D	0.471	neutral	N	0.48581181	None	None	N
K/S	0.3951	ambiguous	0.3839	ambiguous	-1.819	Destabilizing	0.845	D	0.463	neutral	None	None	None	None	N
K/T	0.135	likely_benign	0.1339	benign	-1.384	Destabilizing	0.025	N	0.382	neutral	N	0.464281744	None	None	N
K/V	0.2769	likely_benign	0.2789	benign	-0.138	Destabilizing	0.95	D	0.713	prob.delet.	None	None	None	None	N
K/W	0.7231	likely_pathogenic	0.7114	pathogenic	-0.25	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
K/Y	0.5712	likely_pathogenic	0.5422	ambiguous	0.04	Stabilizing	0.996	D	0.783	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.