TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19099	57520;57521;57522	chr2:178597787;178597786;178597785	chr2:179462514;179462513;179462512
N2AB	17458	52597;52598;52599	chr2:178597787;178597786;178597785	chr2:179462514;179462513;179462512
N2A	16531	49816;49817;49818	chr2:178597787;178597786;178597785	chr2:179462514;179462513;179462512
N2B	10034	30325;30326;30327	chr2:178597787;178597786;178597785	chr2:179462514;179462513;179462512
Novex-1	10159	30700;30701;30702	chr2:178597787;178597786;178597785	chr2:179462514;179462513;179462512
Novex-2	10226	30901;30902;30903	chr2:178597787;178597786;178597785	chr2:179462514;179462513;179462512
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-117
• Domain position: 5
• Structural Position: 8
• Q(SASA): 0.5607
• 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
R/G	None	None	0.324	N	0.441	0.189	0.282575091529	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
R/A	0.7731	likely_pathogenic	0.8071	pathogenic	0.035	Stabilizing	0.116	N	0.425	neutral	None	None	None	None	I
R/C	0.6156	likely_pathogenic	0.6124	pathogenic	-0.157	Destabilizing	0.981	D	0.386	neutral	None	None	None	None	I
R/D	0.9308	likely_pathogenic	0.9432	pathogenic	-0.042	Destabilizing	0.388	N	0.409	neutral	None	None	None	None	I
R/E	0.7663	likely_pathogenic	0.7906	pathogenic	0.022	Stabilizing	0.116	N	0.394	neutral	None	None	None	None	I
R/F	0.91	likely_pathogenic	0.9183	pathogenic	-0.199	Destabilizing	0.932	D	0.396	neutral	None	None	None	None	I
R/G	0.6092	likely_pathogenic	0.6567	pathogenic	-0.156	Destabilizing	0.324	N	0.441	neutral	N	0.476584612	None	None	I
R/H	0.3052	likely_benign	0.2907	benign	-0.66	Destabilizing	0.818	D	0.414	neutral	None	None	None	None	I
R/I	0.7545	likely_pathogenic	0.7826	pathogenic	0.5	Stabilizing	0.773	D	0.401	neutral	N	0.480711898	None	None	I
R/K	0.112	likely_benign	0.1285	benign	-0.045	Destabilizing	None	N	0.185	neutral	N	0.400390555	None	None	I
R/L	0.6719	likely_pathogenic	0.6818	pathogenic	0.5	Stabilizing	0.388	N	0.441	neutral	None	None	None	None	I
R/M	0.6882	likely_pathogenic	0.7081	pathogenic	0.04	Stabilizing	0.932	D	0.395	neutral	None	None	None	None	I
R/N	0.8681	likely_pathogenic	0.8901	pathogenic	0.134	Stabilizing	0.388	N	0.395	neutral	None	None	None	None	I
R/P	0.8881	likely_pathogenic	0.8928	pathogenic	0.365	Stabilizing	0.563	D	0.403	neutral	None	None	None	None	I
R/Q	0.225	likely_benign	0.232	benign	0.06	Stabilizing	0.241	N	0.421	neutral	None	None	None	None	I
R/S	0.8354	likely_pathogenic	0.8568	pathogenic	-0.19	Destabilizing	0.09	N	0.434	neutral	N	0.507096733	None	None	I
R/T	0.6583	likely_pathogenic	0.6725	pathogenic	0.007	Stabilizing	0.324	N	0.427	neutral	N	0.518911237	None	None	I
R/V	0.7697	likely_pathogenic	0.7964	pathogenic	0.365	Stabilizing	0.388	N	0.427	neutral	None	None	None	None	I
R/W	0.6112	likely_pathogenic	0.5834	pathogenic	-0.278	Destabilizing	0.981	D	0.408	neutral	None	None	None	None	I
R/Y	0.8335	likely_pathogenic	0.8329	pathogenic	0.14	Stabilizing	0.932	D	0.392	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.