TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22906	68941;68942;68943	chr2:178577710;178577709;178577708	chr2:179442437;179442436;179442435
N2AB	21265	64018;64019;64020	chr2:178577710;178577709;178577708	chr2:179442437;179442436;179442435
N2A	20338	61237;61238;61239	chr2:178577710;178577709;178577708	chr2:179442437;179442436;179442435
N2B	13841	41746;41747;41748	chr2:178577710;178577709;178577708	chr2:179442437;179442436;179442435
Novex-1	13966	42121;42122;42123	chr2:178577710;178577709;178577708	chr2:179442437;179442436;179442435
Novex-2	14033	42322;42323;42324	chr2:178577710;178577709;178577708	chr2:179442437;179442436;179442435
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: Fn3-54
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1222
• 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	1.0	D	0.869	0.865	0.891955713682	gnomAD-4.0.0	6.84395E-07	None	None	None	None	N	None	2.98882E-05	0	None	0	0	None	0	0	0	0	0
L/I	None	None	0.999	D	0.831	0.784	0.862389191728	gnomAD-4.0.0	2.05319E-06	None	None	None	None	N	None	2.98882E-05	0	None	0	0	None	0	0	1.79923E-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	0.9136	likely_pathogenic	0.9251	pathogenic	-2.411	Highly Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
L/C	0.8433	likely_pathogenic	0.865	pathogenic	-2.089	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9989	pathogenic	-1.997	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/E	0.9945	likely_pathogenic	0.9952	pathogenic	-1.911	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/F	0.7957	likely_pathogenic	0.8359	pathogenic	-1.808	Destabilizing	1.0	D	0.869	deleterious	D	0.661725936	None	None	N
L/G	0.9856	likely_pathogenic	0.9866	pathogenic	-2.829	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/H	0.9876	likely_pathogenic	0.9889	pathogenic	-1.964	Destabilizing	1.0	D	0.812	deleterious	D	0.688071265	None	None	N
L/I	0.2813	likely_benign	0.3293	benign	-1.274	Destabilizing	0.999	D	0.831	deleterious	D	0.635178803	None	None	N
L/K	0.9907	likely_pathogenic	0.9913	pathogenic	-1.738	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/M	0.3843	ambiguous	0.4307	ambiguous	-1.188	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/N	0.9894	likely_pathogenic	0.9908	pathogenic	-1.775	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/P	0.9928	likely_pathogenic	0.9945	pathogenic	-1.626	Destabilizing	1.0	D	0.857	deleterious	D	0.67181974	None	None	N
L/Q	0.9809	likely_pathogenic	0.9834	pathogenic	-1.885	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/R	0.9778	likely_pathogenic	0.9786	pathogenic	-1.151	Destabilizing	1.0	D	0.853	deleterious	D	0.67181974	None	None	N
L/S	0.9879	likely_pathogenic	0.9905	pathogenic	-2.557	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/T	0.9094	likely_pathogenic	0.9211	pathogenic	-2.329	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/V	0.3341	likely_benign	0.3697	ambiguous	-1.626	Destabilizing	0.999	D	0.84	deleterious	D	0.600696993	None	None	N
L/W	0.9859	likely_pathogenic	0.9883	pathogenic	-1.883	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/Y	0.9814	likely_pathogenic	0.985	pathogenic	-1.666	Destabilizing	1.0	D	0.831	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.