TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14649	44170;44171;44172	chr2:178631103;178631102;178631101	chr2:179495830;179495829;179495828
N2AB	13008	39247;39248;39249	chr2:178631103;178631102;178631101	chr2:179495830;179495829;179495828
N2A	12081	36466;36467;36468	chr2:178631103;178631102;178631101	chr2:179495830;179495829;179495828
N2B	5584	16975;16976;16977	chr2:178631103;178631102;178631101	chr2:179495830;179495829;179495828
Novex-1	5709	17350;17351;17352	chr2:178631103;178631102;178631101	chr2:179495830;179495829;179495828
Novex-2	5776	17551;17552;17553	chr2:178631103;178631102;178631101	chr2:179495830;179495829;179495828
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-97
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.6637
• 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	0.998	N	0.415	0.206	0.190952846119	gnomAD-4.0.0	6.84385E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99593E-07	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	0.5411	ambiguous	0.4574	ambiguous	-0.002	Destabilizing	0.992	D	0.453	neutral	None	None	None	None	N
K/C	0.8996	likely_pathogenic	0.8673	pathogenic	-0.238	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
K/D	0.8128	likely_pathogenic	0.7504	pathogenic	0.102	Stabilizing	0.999	D	0.401	neutral	None	None	None	None	N
K/E	0.341	ambiguous	0.2836	benign	0.122	Stabilizing	0.978	D	0.455	neutral	N	0.440089969	None	None	N
K/F	0.8693	likely_pathogenic	0.8342	pathogenic	-0.134	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
K/G	0.7229	likely_pathogenic	0.6529	pathogenic	-0.222	Destabilizing	0.996	D	0.419	neutral	None	None	None	None	N
K/H	0.4794	ambiguous	0.4263	ambiguous	-0.474	Destabilizing	1.0	D	0.455	neutral	None	None	None	None	N
K/I	0.5213	ambiguous	0.4507	ambiguous	0.502	Stabilizing	0.999	D	0.581	neutral	N	0.429276145	None	None	N
K/L	0.4653	ambiguous	0.4176	ambiguous	0.502	Stabilizing	0.996	D	0.419	neutral	None	None	None	None	N
K/M	0.4005	ambiguous	0.3576	ambiguous	0.217	Stabilizing	1.0	D	0.455	neutral	None	None	None	None	N
K/N	0.6362	likely_pathogenic	0.5485	ambiguous	0.171	Stabilizing	0.998	D	0.415	neutral	N	0.454892936	None	None	N
K/P	0.5689	likely_pathogenic	0.549	ambiguous	0.363	Stabilizing	1.0	D	0.455	neutral	None	None	None	None	N
K/Q	0.2145	likely_benign	0.1864	benign	0.023	Stabilizing	0.889	D	0.296	neutral	N	0.452324489	None	None	N
K/R	0.1048	likely_benign	0.0983	benign	-0.089	Destabilizing	0.217	N	0.338	neutral	N	0.447595878	None	None	N
K/S	0.6614	likely_pathogenic	0.5707	pathogenic	-0.324	Destabilizing	0.992	D	0.432	neutral	None	None	None	None	N
K/T	0.3777	ambiguous	0.3117	benign	-0.15	Destabilizing	0.998	D	0.392	neutral	N	0.448302217	None	None	N
K/V	0.5397	ambiguous	0.461	ambiguous	0.363	Stabilizing	0.999	D	0.486	neutral	None	None	None	None	N
K/W	0.8923	likely_pathogenic	0.8657	pathogenic	-0.145	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
K/Y	0.7815	likely_pathogenic	0.7301	pathogenic	0.2	Stabilizing	1.0	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.