TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30779	92560;92561;92562	chr2:178549291;178549290;178549289	chr2:179414018;179414017;179414016
N2AB	29138	87637;87638;87639	chr2:178549291;178549290;178549289	chr2:179414018;179414017;179414016
N2A	28211	84856;84857;84858	chr2:178549291;178549290;178549289	chr2:179414018;179414017;179414016
N2B	21714	65365;65366;65367	chr2:178549291;178549290;178549289	chr2:179414018;179414017;179414016
Novex-1	21839	65740;65741;65742	chr2:178549291;178549290;178549289	chr2:179414018;179414017;179414016
Novex-2	21906	65941;65942;65943	chr2:178549291;178549290;178549289	chr2:179414018;179414017;179414016
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: Fn3-112
• Domain position: 61
• Structural Position: 90
• Q(SASA): 0.5002
• Predicted PPI site: N

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/T	rs1289817129	None	1.0	N	0.709	0.341	0.520640030592	gnomAD-4.0.0	3.18207E-06	None	None	None	None	N	None	0	0	None	0	5.5457E-05	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
R/A	0.7379	likely_pathogenic	0.7213	pathogenic	-0.437	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
R/C	0.2526	likely_benign	0.2374	benign	-0.456	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
R/D	0.9146	likely_pathogenic	0.9116	pathogenic	0.112	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
R/E	0.7423	likely_pathogenic	0.7351	pathogenic	0.218	Stabilizing	0.999	D	0.658	neutral	None	None	None	None	N
R/F	0.774	likely_pathogenic	0.7606	pathogenic	-0.422	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/G	0.6315	likely_pathogenic	0.6023	pathogenic	-0.704	Destabilizing	1.0	D	0.642	neutral	N	0.494690506	None	None	N
R/H	0.1568	likely_benign	0.1469	benign	-1.094	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
R/I	0.5576	ambiguous	0.5217	ambiguous	0.259	Stabilizing	1.0	D	0.735	prob.delet.	N	0.480055745	None	None	N
R/K	0.2534	likely_benign	0.2219	benign	-0.372	Destabilizing	0.997	D	0.542	neutral	N	0.469242417	None	None	N
R/L	0.5636	ambiguous	0.5233	ambiguous	0.259	Stabilizing	1.0	D	0.642	neutral	None	None	None	None	N
R/M	0.6261	likely_pathogenic	0.5904	pathogenic	-0.158	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
R/N	0.8048	likely_pathogenic	0.7953	pathogenic	0.017	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
R/P	0.976	likely_pathogenic	0.9718	pathogenic	0.049	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
R/Q	0.2084	likely_benign	0.194	benign	-0.12	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/S	0.7255	likely_pathogenic	0.7218	pathogenic	-0.621	Destabilizing	1.0	D	0.723	prob.delet.	N	0.472474366	None	None	N
R/T	0.5109	ambiguous	0.487	ambiguous	-0.346	Destabilizing	1.0	D	0.709	prob.delet.	N	0.494871223	None	None	N
R/V	0.5967	likely_pathogenic	0.5812	pathogenic	0.049	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
R/W	0.3456	ambiguous	0.3179	benign	-0.238	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
R/Y	0.5402	ambiguous	0.5305	ambiguous	0.104	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N

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.