TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35302	106129;106130;106131	chr2:178530711;178530710;178530709	chr2:179395438;179395437;179395436
N2AB	33661	101206;101207;101208	chr2:178530711;178530710;178530709	chr2:179395438;179395437;179395436
N2A	32734	98425;98426;98427	chr2:178530711;178530710;178530709	chr2:179395438;179395437;179395436
N2B	26237	78934;78935;78936	chr2:178530711;178530710;178530709	chr2:179395438;179395437;179395436
Novex-1	26362	79309;79310;79311	chr2:178530711;178530710;178530709	chr2:179395438;179395437;179395436
Novex-2	26429	79510;79511;79512	chr2:178530711;178530710;178530709	chr2:179395438;179395437;179395436
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: Ig-165
• Domain position: 17
• Structural Position: 29
• Q(SASA): 0.4532
• 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/N	None	None	0.98	N	0.543	0.16	0.12205267543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.5682	likely_pathogenic	0.5023	ambiguous	-0.775	Destabilizing	0.97	D	0.553	neutral	None	None	None	None	N
K/C	0.8402	likely_pathogenic	0.8132	pathogenic	-1.116	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.8599	likely_pathogenic	0.8021	pathogenic	-1.094	Destabilizing	0.97	D	0.573	neutral	None	None	None	None	N
K/E	0.3584	ambiguous	0.3034	benign	-0.946	Destabilizing	0.835	D	0.588	neutral	N	0.444614895	None	None	N
K/F	0.8717	likely_pathogenic	0.8345	pathogenic	-0.407	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
K/G	0.7395	likely_pathogenic	0.6627	pathogenic	-1.17	Destabilizing	0.985	D	0.601	neutral	None	None	None	None	N
K/H	0.4352	ambiguous	0.406	ambiguous	-1.535	Destabilizing	0.996	D	0.65	neutral	None	None	None	None	N
K/I	0.4491	ambiguous	0.383	ambiguous	0.273	Stabilizing	0.998	D	0.702	prob.neutral	N	0.425221058	None	None	N
K/L	0.5125	ambiguous	0.4641	ambiguous	0.273	Stabilizing	0.97	D	0.601	neutral	None	None	None	None	N
K/M	0.3687	ambiguous	0.3198	benign	0.119	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
K/N	0.6151	likely_pathogenic	0.5384	ambiguous	-1.101	Destabilizing	0.98	D	0.543	neutral	N	0.468569191	None	None	N
K/P	0.985	likely_pathogenic	0.9744	pathogenic	-0.048	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
K/Q	0.2263	likely_benign	0.2073	benign	-1.142	Destabilizing	0.489	N	0.41	neutral	N	0.462104578	None	None	N
K/R	0.114	likely_benign	0.1064	benign	-0.952	Destabilizing	0.031	N	0.249	neutral	N	0.450655433	None	None	N
K/S	0.5868	likely_pathogenic	0.523	ambiguous	-1.656	Destabilizing	0.97	D	0.555	neutral	None	None	None	None	N
K/T	0.2432	likely_benign	0.2123	benign	-1.297	Destabilizing	0.98	D	0.565	neutral	N	0.422233894	None	None	N
K/V	0.4244	ambiguous	0.3713	ambiguous	-0.048	Destabilizing	0.996	D	0.644	neutral	None	None	None	None	N
K/W	0.8976	likely_pathogenic	0.8735	pathogenic	-0.365	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/Y	0.7866	likely_pathogenic	0.7338	pathogenic	0.001	Stabilizing	0.999	D	0.678	prob.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.