TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6458	19597;19598;19599	chr2:178728554;178728553;178728552	chr2:179593281;179593280;179593279
N2AB	6141	18646;18647;18648	chr2:178728554;178728553;178728552	chr2:179593281;179593280;179593279
N2A	5214	15865;15866;15867	chr2:178728554;178728553;178728552	chr2:179593281;179593280;179593279
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-48
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3685
• 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	None	None	0.961	N	0.553	0.265	0.380564188046	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.4044	ambiguous	0.3587	ambiguous	-1.031	Destabilizing	0.97	D	0.629	neutral	None	None	None	None	N
K/C	0.6677	likely_pathogenic	0.6635	pathogenic	-1.157	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/D	0.7703	likely_pathogenic	0.6899	pathogenic	-0.284	Destabilizing	0.942	D	0.629	neutral	None	None	None	None	N
K/E	0.1785	likely_benign	0.1332	benign	-0.107	Destabilizing	0.044	N	0.355	neutral	N	0.383757383	None	None	N
K/F	0.7689	likely_pathogenic	0.7128	pathogenic	-0.574	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
K/G	0.7367	likely_pathogenic	0.6918	pathogenic	-1.437	Destabilizing	0.985	D	0.713	prob.delet.	None	None	None	None	N
K/H	0.2804	likely_benign	0.2593	benign	-1.581	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
K/I	0.2323	likely_benign	0.1899	benign	0.055	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
K/L	0.3021	likely_benign	0.261	benign	0.055	Stabilizing	0.985	D	0.743	deleterious	None	None	None	None	N
K/M	0.1683	likely_benign	0.1471	benign	-0.179	Destabilizing	1.0	D	0.693	prob.neutral	N	0.487847329	None	None	N
K/N	0.5596	ambiguous	0.4689	ambiguous	-0.768	Destabilizing	0.98	D	0.563	neutral	N	0.499101686	None	None	N
K/P	0.985	likely_pathogenic	0.9794	pathogenic	-0.28	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
K/Q	0.1087	likely_benign	0.098	benign	-0.77	Destabilizing	0.961	D	0.578	neutral	N	0.446728639	None	None	N
K/R	0.0855	likely_benign	0.085	benign	-0.614	Destabilizing	0.961	D	0.553	neutral	N	0.470490933	None	None	N
K/S	0.454	ambiguous	0.3966	ambiguous	-1.569	Destabilizing	0.97	D	0.549	neutral	None	None	None	None	N
K/T	0.1395	likely_benign	0.1132	benign	-1.157	Destabilizing	0.98	D	0.663	neutral	N	0.468624064	None	None	N
K/V	0.2184	likely_benign	0.1877	benign	-0.28	Destabilizing	0.996	D	0.754	deleterious	None	None	None	None	N
K/W	0.7585	likely_pathogenic	0.733	pathogenic	-0.375	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/Y	0.6548	likely_pathogenic	0.6046	pathogenic	-0.072	Destabilizing	0.999	D	0.767	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.