TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20159	60700;60701;60702	chr2:178591250;178591249;178591248	chr2:179455977;179455976;179455975
N2AB	18518	55777;55778;55779	chr2:178591250;178591249;178591248	chr2:179455977;179455976;179455975
N2A	17591	52996;52997;52998	chr2:178591250;178591249;178591248	chr2:179455977;179455976;179455975
N2B	11094	33505;33506;33507	chr2:178591250;178591249;178591248	chr2:179455977;179455976;179455975
Novex-1	11219	33880;33881;33882	chr2:178591250;178591249;178591248	chr2:179455977;179455976;179455975
Novex-2	11286	34081;34082;34083	chr2:178591250;178591249;178591248	chr2:179455977;179455976;179455975
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-120
• Domain position: 80
• Structural Position: 165
• Q(SASA): 0.4112
• 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
S/N	rs1005693391	None	0.22	D	0.411	0.093	0.165133752707	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0925	likely_benign	0.0903	benign	-0.349	Destabilizing	0.072	N	0.395	neutral	None	None	None	None	I
S/C	0.1079	likely_benign	0.1079	benign	-0.193	Destabilizing	0.883	D	0.543	neutral	D	0.530058502	None	None	I
S/D	0.3591	ambiguous	0.4254	ambiguous	0.055	Stabilizing	0.272	N	0.396	neutral	None	None	None	None	I
S/E	0.3233	likely_benign	0.3702	ambiguous	-0.06	Destabilizing	0.272	N	0.361	neutral	None	None	None	None	I
S/F	0.1682	likely_benign	0.1857	benign	-1.111	Destabilizing	0.726	D	0.643	neutral	None	None	None	None	I
S/G	0.1144	likely_benign	0.1201	benign	-0.394	Destabilizing	0.22	N	0.339	neutral	N	0.499583984	None	None	I
S/H	0.2638	likely_benign	0.2828	benign	-0.978	Destabilizing	0.003	N	0.399	neutral	None	None	None	None	I
S/I	0.1288	likely_benign	0.1409	benign	-0.357	Destabilizing	0.331	N	0.633	neutral	N	0.491950661	None	None	I
S/K	0.402	ambiguous	0.4567	ambiguous	-0.337	Destabilizing	0.272	N	0.397	neutral	None	None	None	None	I
S/L	0.0929	likely_benign	0.0963	benign	-0.357	Destabilizing	0.157	N	0.562	neutral	None	None	None	None	I
S/M	0.1469	likely_benign	0.1324	benign	-0.01	Destabilizing	0.909	D	0.521	neutral	None	None	None	None	I
S/N	0.1085	likely_benign	0.1193	benign	-0.047	Destabilizing	0.22	N	0.411	neutral	D	0.523901343	None	None	I
S/P	0.6438	likely_pathogenic	0.745	pathogenic	-0.331	Destabilizing	0.726	D	0.505	neutral	None	None	None	None	I
S/Q	0.314	likely_benign	0.3246	benign	-0.333	Destabilizing	0.567	D	0.446	neutral	None	None	None	None	I
S/R	0.3762	ambiguous	0.4302	ambiguous	-0.172	Destabilizing	0.497	N	0.483	neutral	D	0.524632062	None	None	I
S/T	0.0592	likely_benign	0.0576	benign	-0.16	Destabilizing	None	N	0.139	neutral	N	0.462506168	None	None	I
S/V	0.135	likely_benign	0.1319	benign	-0.331	Destabilizing	0.157	N	0.572	neutral	None	None	None	None	I
S/W	0.3347	likely_benign	0.3698	ambiguous	-1.14	Destabilizing	0.968	D	0.694	prob.neutral	None	None	None	None	I
S/Y	0.1713	likely_benign	0.1869	benign	-0.847	Destabilizing	0.567	D	0.645	neutral	None	None	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.