TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19706	59341;59342;59343	chr2:178593003;178593002;178593001	chr2:179457730;179457729;179457728
N2AB	18065	54418;54419;54420	chr2:178593003;178593002;178593001	chr2:179457730;179457729;179457728
N2A	17138	51637;51638;51639	chr2:178593003;178593002;178593001	chr2:179457730;179457729;179457728
N2B	10641	32146;32147;32148	chr2:178593003;178593002;178593001	chr2:179457730;179457729;179457728
Novex-1	10766	32521;32522;32523	chr2:178593003;178593002;178593001	chr2:179457730;179457729;179457728
Novex-2	10833	32722;32723;32724	chr2:178593003;178593002;178593001	chr2:179457730;179457729;179457728
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-31
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5174
• Predicted PPI site: I

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
H/D	None	None	None	N	0.099	0.244	0.183819452728	gnomAD-4.0.0	1.20036E-06	None	None	None	None	I	None	6.33633E-05	0	None	0	0	None	0	0	0	0	0
H/L	None	None	0.117	N	0.47	0.182	0.238096912614	gnomAD-4.0.0	1.20035E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31253E-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
H/A	0.4684	ambiguous	0.3969	ambiguous	0.405	Stabilizing	0.067	N	0.365	neutral	None	None	None	None	I
H/C	0.2742	likely_benign	0.2302	benign	0.651	Stabilizing	0.935	D	0.343	neutral	None	None	None	None	I
H/D	0.3527	ambiguous	0.2872	benign	0.128	Stabilizing	None	N	0.099	neutral	N	0.399456688	None	None	I
H/E	0.4357	ambiguous	0.3734	ambiguous	0.121	Stabilizing	0.035	N	0.325	neutral	None	None	None	None	I
H/F	0.2984	likely_benign	0.2964	benign	0.747	Stabilizing	0.555	D	0.344	neutral	None	None	None	None	I
H/G	0.46	ambiguous	0.3887	ambiguous	0.186	Stabilizing	0.067	N	0.371	neutral	None	None	None	None	I
H/I	0.4628	ambiguous	0.4138	ambiguous	0.931	Stabilizing	0.555	D	0.427	neutral	None	None	None	None	I
H/K	0.331	likely_benign	0.2562	benign	0.383	Stabilizing	0.035	N	0.331	neutral	None	None	None	None	I
H/L	0.2271	likely_benign	0.1868	benign	0.931	Stabilizing	0.117	N	0.47	neutral	N	0.511491327	None	None	I
H/M	0.5266	ambiguous	0.4795	ambiguous	0.744	Stabilizing	0.935	D	0.346	neutral	None	None	None	None	I
H/N	0.1827	likely_benign	0.1572	benign	0.423	Stabilizing	0.052	N	0.319	neutral	N	0.470818141	None	None	I
H/P	0.7129	likely_pathogenic	0.6461	pathogenic	0.78	Stabilizing	0.484	N	0.404	neutral	N	0.5071443	None	None	I
H/Q	0.264	likely_benign	0.2192	benign	0.445	Stabilizing	0.117	N	0.327	neutral	N	0.503853279	None	None	I
H/R	0.1649	likely_benign	0.1239	benign	-0.019	Destabilizing	None	N	0.137	neutral	N	0.476821393	None	None	I
H/S	0.3643	ambiguous	0.3068	benign	0.446	Stabilizing	0.067	N	0.328	neutral	None	None	None	None	I
H/T	0.4249	ambiguous	0.3575	ambiguous	0.531	Stabilizing	0.149	N	0.421	neutral	None	None	None	None	I
H/V	0.3829	ambiguous	0.3293	benign	0.78	Stabilizing	0.149	N	0.451	neutral	None	None	None	None	I
H/W	0.3557	ambiguous	0.3367	benign	0.636	Stabilizing	0.935	D	0.387	neutral	None	None	None	None	I
H/Y	0.1125	likely_benign	0.1135	benign	0.994	Stabilizing	0.211	N	0.339	neutral	N	0.43487877	None	None	I

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.