TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14594	44005;44006;44007	chr2:178631268;178631267;178631266	chr2:179495995;179495994;179495993
N2AB	12953	39082;39083;39084	chr2:178631268;178631267;178631266	chr2:179495995;179495994;179495993
N2A	12026	36301;36302;36303	chr2:178631268;178631267;178631266	chr2:179495995;179495994;179495993
N2B	5529	16810;16811;16812	chr2:178631268;178631267;178631266	chr2:179495995;179495994;179495993
Novex-1	5654	17185;17186;17187	chr2:178631268;178631267;178631266	chr2:179495995;179495994;179495993
Novex-2	5721	17386;17387;17388	chr2:178631268;178631267;178631266	chr2:179495995;179495994;179495993
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-97
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6771
• 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
D/G	None	None	0.996	D	0.511	0.492	0.210429274316	gnomAD-4.0.0	3.19667E-06	None	None	None	None	N	None	0	4.59179E-05	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
D/A	0.4265	ambiguous	0.5377	ambiguous	-0.148	Destabilizing	0.999	D	0.603	neutral	D	0.541843204	None	None	N
D/C	0.902	likely_pathogenic	0.9424	pathogenic	0.121	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
D/E	0.5182	ambiguous	0.6044	pathogenic	-0.23	Destabilizing	0.996	D	0.391	neutral	D	0.543283829	None	None	N
D/F	0.9235	likely_pathogenic	0.9545	pathogenic	-0.205	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
D/G	0.2999	likely_benign	0.3646	ambiguous	-0.313	Destabilizing	0.996	D	0.511	neutral	D	0.548485025	None	None	N
D/H	0.6242	likely_pathogenic	0.7281	pathogenic	0.003	Stabilizing	1.0	D	0.647	neutral	D	0.573146203	None	None	N
D/I	0.8227	likely_pathogenic	0.8965	pathogenic	0.226	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
D/K	0.7659	likely_pathogenic	0.8514	pathogenic	0.446	Stabilizing	0.999	D	0.656	neutral	None	None	None	None	N
D/L	0.8361	likely_pathogenic	0.9045	pathogenic	0.226	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
D/M	0.9475	likely_pathogenic	0.9687	pathogenic	0.297	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
D/N	0.1355	likely_benign	0.1667	benign	0.22	Stabilizing	0.767	D	0.254	neutral	N	0.45499792	None	None	N
D/P	0.7655	likely_pathogenic	0.8388	pathogenic	0.123	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
D/Q	0.7925	likely_pathogenic	0.8681	pathogenic	0.236	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
D/R	0.793	likely_pathogenic	0.8748	pathogenic	0.553	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
D/S	0.2571	likely_benign	0.318	benign	0.124	Stabilizing	0.997	D	0.487	neutral	None	None	None	None	N
D/T	0.6216	likely_pathogenic	0.7	pathogenic	0.25	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	N
D/V	0.6427	likely_pathogenic	0.7602	pathogenic	0.123	Stabilizing	1.0	D	0.681	prob.neutral	D	0.565415076	None	None	N
D/W	0.9817	likely_pathogenic	0.9878	pathogenic	-0.125	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
D/Y	0.4943	ambiguous	0.6298	pathogenic	0.024	Stabilizing	1.0	D	0.659	neutral	D	0.695731195	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.