TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23515	70768;70769;70770	chr2:178575589;178575588;178575587	chr2:179440316;179440315;179440314
N2AB	21874	65845;65846;65847	chr2:178575589;178575588;178575587	chr2:179440316;179440315;179440314
N2A	20947	63064;63065;63066	chr2:178575589;178575588;178575587	chr2:179440316;179440315;179440314
N2B	14450	43573;43574;43575	chr2:178575589;178575588;178575587	chr2:179440316;179440315;179440314
Novex-1	14575	43948;43949;43950	chr2:178575589;178575588;178575587	chr2:179440316;179440315;179440314
Novex-2	14642	44149;44150;44151	chr2:178575589;178575588;178575587	chr2:179440316;179440315;179440314
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-58
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.7935
• 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
Y/C	None	None	0.952	N	0.467	0.304	0.394837016283	gnomAD-4.0.0	8.89535E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.16941E-05	0	0
Y/D	None	None	0.952	N	0.494	0.359	0.588141112584	gnomAD-4.0.0	1.59154E-06	None	None	None	None	I	None	5.65739E-05	0	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
Y/A	0.889	likely_pathogenic	0.9287	pathogenic	-0.673	Destabilizing	0.332	N	0.461	neutral	None	None	None	None	I
Y/C	0.4104	ambiguous	0.563	ambiguous	0.112	Stabilizing	0.952	D	0.467	neutral	N	0.473659736	None	None	I
Y/D	0.9258	likely_pathogenic	0.9397	pathogenic	0.981	Stabilizing	0.952	D	0.494	neutral	N	0.510625033	None	None	I
Y/E	0.9656	likely_pathogenic	0.9763	pathogenic	0.955	Stabilizing	0.882	D	0.522	neutral	None	None	None	None	I
Y/F	0.0863	likely_benign	0.0929	benign	-0.391	Destabilizing	None	N	0.157	neutral	N	0.481539354	None	None	I
Y/G	0.9145	likely_pathogenic	0.9401	pathogenic	-0.853	Destabilizing	0.71	D	0.521	neutral	None	None	None	None	I
Y/H	0.6142	likely_pathogenic	0.693	pathogenic	0.213	Stabilizing	0.855	D	0.377	neutral	N	0.511283471	None	None	I
Y/I	0.5802	likely_pathogenic	0.7003	pathogenic	-0.232	Destabilizing	0.01	N	0.413	neutral	None	None	None	None	I
Y/K	0.9617	likely_pathogenic	0.9757	pathogenic	0.28	Stabilizing	0.228	N	0.505	neutral	None	None	None	None	I
Y/L	0.6854	likely_pathogenic	0.7481	pathogenic	-0.232	Destabilizing	None	N	0.183	neutral	None	None	None	None	I
Y/M	0.7306	likely_pathogenic	0.7966	pathogenic	-0.027	Destabilizing	0.014	N	0.272	neutral	None	None	None	None	I
Y/N	0.5644	likely_pathogenic	0.6267	pathogenic	0.125	Stabilizing	0.952	D	0.499	neutral	N	0.469238736	None	None	I
Y/P	0.9959	likely_pathogenic	0.9965	pathogenic	-0.359	Destabilizing	0.963	D	0.484	neutral	None	None	None	None	I
Y/Q	0.9313	likely_pathogenic	0.9573	pathogenic	0.133	Stabilizing	0.72	D	0.467	neutral	None	None	None	None	I
Y/R	0.9348	likely_pathogenic	0.957	pathogenic	0.572	Stabilizing	0.781	D	0.503	neutral	None	None	None	None	I
Y/S	0.8194	likely_pathogenic	0.8782	pathogenic	-0.346	Destabilizing	0.648	D	0.503	neutral	N	0.472961719	None	None	I
Y/T	0.8942	likely_pathogenic	0.936	pathogenic	-0.28	Destabilizing	0.71	D	0.469	neutral	None	None	None	None	I
Y/V	0.5571	ambiguous	0.6769	pathogenic	-0.359	Destabilizing	0.098	N	0.351	neutral	None	None	None	None	I
Y/W	0.6285	likely_pathogenic	0.6888	pathogenic	-0.507	Destabilizing	0.936	D	0.405	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.