TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23300	70123;70124;70125	chr2:178576234;178576233;178576232	chr2:179440961;179440960;179440959
N2AB	21659	65200;65201;65202	chr2:178576234;178576233;178576232	chr2:179440961;179440960;179440959
N2A	20732	62419;62420;62421	chr2:178576234;178576233;178576232	chr2:179440961;179440960;179440959
N2B	14235	42928;42929;42930	chr2:178576234;178576233;178576232	chr2:179440961;179440960;179440959
Novex-1	14360	43303;43304;43305	chr2:178576234;178576233;178576232	chr2:179440961;179440960;179440959
Novex-2	14427	43504;43505;43506	chr2:178576234;178576233;178576232	chr2:179440961;179440960;179440959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-57
• Domain position: 61
• Structural Position: 90
• Q(SASA): 0.5444
• 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
Q/L	None	None	0.024	N	0.467	0.245	0.308278614506	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
Q/A	0.2079	likely_benign	0.2195	benign	-0.5	Destabilizing	0.007	N	0.339	neutral	None	None	None	None	I
Q/C	0.6884	likely_pathogenic	0.6809	pathogenic	-0.099	Destabilizing	0.864	D	0.546	neutral	None	None	None	None	I
Q/D	0.3228	likely_benign	0.3489	ambiguous	-0.099	Destabilizing	None	N	0.217	neutral	None	None	None	None	I
Q/E	0.0545	likely_benign	0.0578	benign	0.013	Stabilizing	None	N	0.172	neutral	N	0.356402131	None	None	I
Q/F	0.8442	likely_pathogenic	0.8485	pathogenic	-0.275	Destabilizing	0.628	D	0.552	neutral	None	None	None	None	I
Q/G	0.3021	likely_benign	0.323	benign	-0.831	Destabilizing	0.031	N	0.411	neutral	None	None	None	None	I
Q/H	0.2208	likely_benign	0.2119	benign	-0.37	Destabilizing	0.295	N	0.436	neutral	N	0.45789449	None	None	I
Q/I	0.5947	likely_pathogenic	0.5916	pathogenic	0.338	Stabilizing	0.356	N	0.596	neutral	None	None	None	None	I
Q/K	0.126	likely_benign	0.1247	benign	-0.037	Destabilizing	None	N	0.191	neutral	N	0.436287067	None	None	I
Q/L	0.2644	likely_benign	0.2774	benign	0.338	Stabilizing	0.024	N	0.467	neutral	N	0.493719217	None	None	I
Q/M	0.4657	ambiguous	0.4659	ambiguous	0.382	Stabilizing	0.628	D	0.443	neutral	None	None	None	None	I
Q/N	0.2463	likely_benign	0.2553	benign	-0.706	Destabilizing	0.031	N	0.329	neutral	None	None	None	None	I
Q/P	0.7496	likely_pathogenic	0.7715	pathogenic	0.089	Stabilizing	0.106	N	0.46	neutral	N	0.478096404	None	None	I
Q/R	0.132	likely_benign	0.1334	benign	0.066	Stabilizing	0.012	N	0.344	neutral	N	0.437940505	None	None	I
Q/S	0.1842	likely_benign	0.1931	benign	-0.827	Destabilizing	0.007	N	0.297	neutral	None	None	None	None	I
Q/T	0.1766	likely_benign	0.1746	benign	-0.514	Destabilizing	0.031	N	0.399	neutral	None	None	None	None	I
Q/V	0.3401	ambiguous	0.3369	benign	0.089	Stabilizing	0.072	N	0.511	neutral	None	None	None	None	I
Q/W	0.7475	likely_pathogenic	0.7452	pathogenic	-0.184	Destabilizing	0.864	D	0.57	neutral	None	None	None	None	I
Q/Y	0.5495	ambiguous	0.5534	ambiguous	0.083	Stabilizing	0.628	D	0.565	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.