TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15153	45682;45683;45684	chr2:178621261;178621260;178621259	chr2:179485988;179485987;179485986
N2AB	13512	40759;40760;40761	chr2:178621261;178621260;178621259	chr2:179485988;179485987;179485986
N2A	12585	37978;37979;37980	chr2:178621261;178621260;178621259	chr2:179485988;179485987;179485986
N2B	6088	18487;18488;18489	chr2:178621261;178621260;178621259	chr2:179485988;179485987;179485986
Novex-1	6213	18862;18863;18864	chr2:178621261;178621260;178621259	chr2:179485988;179485987;179485986
Novex-2	6280	19063;19064;19065	chr2:178621261;178621260;178621259	chr2:179485988;179485987;179485986
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-103
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.1726
• 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	rs2154211745	None	0.784	N	0.484	0.164	0.152612264143	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs2154211745	None	0.784	N	0.484	0.164	0.152612264143	gnomAD-4.0.0	6.5799E-06	None	None	None	None	N	None	2.40894E-05	0	None	0	0	None	0	0	0	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	0.5903	likely_pathogenic	0.5626	ambiguous	-0.827	Destabilizing	0.176	N	0.375	neutral	None	None	None	None	N
K/C	0.7778	likely_pathogenic	0.7194	pathogenic	-0.949	Destabilizing	0.981	D	0.539	neutral	None	None	None	None	N
K/D	0.8789	likely_pathogenic	0.8614	pathogenic	-0.957	Destabilizing	0.936	D	0.542	neutral	None	None	None	None	N
K/E	0.3092	likely_benign	0.2889	benign	-0.774	Destabilizing	0.784	D	0.484	neutral	N	0.448413155	None	None	N
K/F	0.7034	likely_pathogenic	0.7111	pathogenic	-0.212	Destabilizing	0.007	N	0.428	neutral	None	None	None	None	N
K/G	0.7398	likely_pathogenic	0.7308	pathogenic	-1.273	Destabilizing	0.828	D	0.498	neutral	None	None	None	None	N
K/H	0.3749	ambiguous	0.3668	ambiguous	-1.621	Destabilizing	0.981	D	0.511	neutral	None	None	None	None	N
K/I	0.2812	likely_benign	0.262	benign	0.378	Stabilizing	0.176	N	0.449	neutral	None	None	None	None	N
K/L	0.3172	likely_benign	0.2886	benign	0.378	Stabilizing	0.001	N	0.318	neutral	None	None	None	None	N
K/M	0.182	likely_benign	0.1636	benign	0.218	Stabilizing	0.065	N	0.349	neutral	N	0.443283714	None	None	N
K/N	0.6157	likely_pathogenic	0.6022	pathogenic	-1.184	Destabilizing	0.917	D	0.529	neutral	N	0.450752219	None	None	N
K/P	0.9909	likely_pathogenic	0.9893	pathogenic	0.005	Stabilizing	0.936	D	0.553	neutral	None	None	None	None	N
K/Q	0.14	likely_benign	0.1401	benign	-1.087	Destabilizing	0.784	D	0.521	neutral	N	0.449537786	None	None	N
K/R	0.103	likely_benign	0.1063	benign	-1.103	Destabilizing	0.784	D	0.489	neutral	N	0.425738444	None	None	N
K/S	0.6155	likely_pathogenic	0.5902	pathogenic	-1.75	Destabilizing	0.665	D	0.471	neutral	None	None	None	None	N
K/T	0.2487	likely_benign	0.2277	benign	-1.338	Destabilizing	0.425	N	0.475	neutral	N	0.442839577	None	None	N
K/V	0.3135	likely_benign	0.2826	benign	0.005	Stabilizing	0.003	N	0.362	neutral	None	None	None	None	N
K/W	0.8091	likely_pathogenic	0.7847	pathogenic	-0.193	Destabilizing	0.995	D	0.531	neutral	None	None	None	None	N
K/Y	0.5894	likely_pathogenic	0.6044	pathogenic	0.125	Stabilizing	0.543	D	0.519	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.