TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20602	62029;62030;62031	chr2:178589921;178589920;178589919	chr2:179454648;179454647;179454646
N2AB	18961	57106;57107;57108	chr2:178589921;178589920;178589919	chr2:179454648;179454647;179454646
N2A	18034	54325;54326;54327	chr2:178589921;178589920;178589919	chr2:179454648;179454647;179454646
N2B	11537	34834;34835;34836	chr2:178589921;178589920;178589919	chr2:179454648;179454647;179454646
Novex-1	11662	35209;35210;35211	chr2:178589921;178589920;178589919	chr2:179454648;179454647;179454646
Novex-2	11729	35410;35411;35412	chr2:178589921;178589920;178589919	chr2:179454648;179454647;179454646
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-37
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5688
• 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
T/I	rs1342930607	None	1.0	N	0.823	0.434	0.467839254973	gnomAD-4.0.0	1.5924E-06	None	None	None	None	I	None	0	0	None	0	2.78489E-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
T/A	0.2583	likely_benign	0.2614	benign	-0.708	Destabilizing	0.999	D	0.547	neutral	N	0.507580976	None	None	I
T/C	0.6879	likely_pathogenic	0.6822	pathogenic	-0.455	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
T/D	0.8324	likely_pathogenic	0.8474	pathogenic	-0.49	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
T/E	0.6994	likely_pathogenic	0.707	pathogenic	-0.524	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
T/F	0.6257	likely_pathogenic	0.6307	pathogenic	-0.939	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
T/G	0.6105	likely_pathogenic	0.6303	pathogenic	-0.921	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
T/H	0.6111	likely_pathogenic	0.6357	pathogenic	-1.252	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
T/I	0.3369	likely_benign	0.3156	benign	-0.242	Destabilizing	1.0	D	0.823	deleterious	N	0.507285947	None	None	I
T/K	0.5112	ambiguous	0.5273	ambiguous	-0.741	Destabilizing	1.0	D	0.83	deleterious	N	0.480575951	None	None	I
T/L	0.2238	likely_benign	0.2173	benign	-0.242	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
T/M	0.199	likely_benign	0.1791	benign	0.169	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
T/N	0.3217	likely_benign	0.3433	ambiguous	-0.646	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
T/P	0.8601	likely_pathogenic	0.8469	pathogenic	-0.366	Destabilizing	1.0	D	0.813	deleterious	D	0.527459657	None	None	I
T/Q	0.4882	ambiguous	0.5035	ambiguous	-0.921	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
T/R	0.4628	ambiguous	0.4782	ambiguous	-0.398	Destabilizing	1.0	D	0.809	deleterious	N	0.471132203	None	None	I
T/S	0.2473	likely_benign	0.261	benign	-0.861	Destabilizing	0.999	D	0.566	neutral	N	0.518366945	None	None	I
T/V	0.2583	likely_benign	0.2455	benign	-0.366	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	I
T/W	0.9102	likely_pathogenic	0.909	pathogenic	-0.867	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
T/Y	0.721	likely_pathogenic	0.7227	pathogenic	-0.632	Destabilizing	1.0	D	0.819	deleterious	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.