TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33534	100825;100826;100827	chr2:178536147;178536146;178536145	chr2:179400874;179400873;179400872
N2AB	31893	95902;95903;95904	chr2:178536147;178536146;178536145	chr2:179400874;179400873;179400872
N2A	30966	93121;93122;93123	chr2:178536147;178536146;178536145	chr2:179400874;179400873;179400872
N2B	24469	73630;73631;73632	chr2:178536147;178536146;178536145	chr2:179400874;179400873;179400872
Novex-1	24594	74005;74006;74007	chr2:178536147;178536146;178536145	chr2:179400874;179400873;179400872
Novex-2	24661	74206;74207;74208	chr2:178536147;178536146;178536145	chr2:179400874;179400873;179400872
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-158
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.705
• 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/T	None	None	0.998	N	0.669	0.604	0.509878532422	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	0.7985	likely_pathogenic	0.8198	pathogenic	0.015	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	N
K/C	0.912	likely_pathogenic	0.9169	pathogenic	-0.363	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/D	0.8987	likely_pathogenic	0.9117	pathogenic	-0.037	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
K/E	0.4574	ambiguous	0.5038	ambiguous	-0.014	Destabilizing	0.992	D	0.648	neutral	N	0.475742037	None	None	N
K/F	0.9674	likely_pathogenic	0.9685	pathogenic	-0.153	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
K/G	0.8663	likely_pathogenic	0.8748	pathogenic	-0.186	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
K/H	0.5765	likely_pathogenic	0.6269	pathogenic	-0.341	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
K/I	0.7497	likely_pathogenic	0.7709	pathogenic	0.469	Stabilizing	0.977	D	0.683	prob.neutral	N	0.501872632	None	None	N
K/L	0.7847	likely_pathogenic	0.8011	pathogenic	0.469	Stabilizing	0.982	D	0.625	neutral	None	None	None	None	N
K/M	0.6266	likely_pathogenic	0.6634	pathogenic	0.046	Stabilizing	0.999	D	0.62	neutral	None	None	None	None	N
K/N	0.7319	likely_pathogenic	0.7739	pathogenic	0.018	Stabilizing	0.999	D	0.681	prob.neutral	N	0.477918337	None	None	N
K/P	0.9915	likely_pathogenic	0.9925	pathogenic	0.345	Stabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/Q	0.2555	likely_benign	0.2985	benign	-0.078	Destabilizing	0.994	D	0.663	neutral	N	0.457790994	None	None	N
K/R	0.1018	likely_benign	0.1142	benign	-0.102	Destabilizing	0.987	D	0.57	neutral	N	0.481073286	None	None	N
K/S	0.8128	likely_pathogenic	0.8375	pathogenic	-0.404	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
K/T	0.5799	likely_pathogenic	0.623	pathogenic	-0.232	Destabilizing	0.998	D	0.669	neutral	N	0.498754969	None	None	N
K/V	0.7111	likely_pathogenic	0.7398	pathogenic	0.345	Stabilizing	0.987	D	0.665	neutral	None	None	None	None	N
K/W	0.9616	likely_pathogenic	0.9677	pathogenic	-0.222	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/Y	0.918	likely_pathogenic	0.9288	pathogenic	0.128	Stabilizing	0.997	D	0.635	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.