TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31358	94297;94298;94299	chr2:178547554;178547553;178547552	chr2:179412281;179412280;179412279
N2AB	29717	89374;89375;89376	chr2:178547554;178547553;178547552	chr2:179412281;179412280;179412279
N2A	28790	86593;86594;86595	chr2:178547554;178547553;178547552	chr2:179412281;179412280;179412279
N2B	22293	67102;67103;67104	chr2:178547554;178547553;178547552	chr2:179412281;179412280;179412279
Novex-1	22418	67477;67478;67479	chr2:178547554;178547553;178547552	chr2:179412281;179412280;179412279
Novex-2	22485	67678;67679;67680	chr2:178547554;178547553;178547552	chr2:179412281;179412280;179412279
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-116
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.3955
• 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
L/F	None	None	0.997	N	0.657	0.225	0.651092396515	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
L/A	0.4615	ambiguous	0.4671	ambiguous	-1.204	Destabilizing	0.983	D	0.509	neutral	None	None	None	None	N
L/C	0.6673	likely_pathogenic	0.6706	pathogenic	-0.685	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
L/D	0.9182	likely_pathogenic	0.9206	pathogenic	-0.701	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
L/E	0.6722	likely_pathogenic	0.6734	pathogenic	-0.772	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
L/F	0.442	ambiguous	0.4567	ambiguous	-1.019	Destabilizing	0.997	D	0.657	neutral	N	0.485041019	None	None	N
L/G	0.8245	likely_pathogenic	0.816	pathogenic	-1.435	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
L/H	0.5699	likely_pathogenic	0.5542	ambiguous	-0.647	Destabilizing	1.0	D	0.729	prob.delet.	N	0.493831073	None	None	N
L/I	0.1101	likely_benign	0.1255	benign	-0.688	Destabilizing	0.9	D	0.424	neutral	N	0.468706129	None	None	N
L/K	0.5464	ambiguous	0.5041	ambiguous	-0.775	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
L/M	0.1347	likely_benign	0.14	benign	-0.477	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
L/N	0.6527	likely_pathogenic	0.6643	pathogenic	-0.493	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
L/P	0.4185	ambiguous	0.3784	ambiguous	-0.827	Destabilizing	0.999	D	0.761	deleterious	N	0.435324274	None	None	N
L/Q	0.3709	ambiguous	0.3556	ambiguous	-0.761	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
L/R	0.4643	ambiguous	0.4326	ambiguous	-0.106	Destabilizing	0.999	D	0.747	deleterious	N	0.436073636	None	None	N
L/S	0.6772	likely_pathogenic	0.7073	pathogenic	-1.002	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
L/T	0.3092	likely_benign	0.341	ambiguous	-0.968	Destabilizing	0.983	D	0.627	neutral	None	None	None	None	N
L/V	0.1044	likely_benign	0.111	benign	-0.827	Destabilizing	0.198	N	0.227	neutral	N	0.400691626	None	None	N
L/W	0.6257	likely_pathogenic	0.6097	pathogenic	-1.022	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
L/Y	0.7058	likely_pathogenic	0.7105	pathogenic	-0.807	Destabilizing	0.999	D	0.727	prob.delet.	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.