TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22899	68920;68921;68922	chr2:178577731;178577730;178577729	chr2:179442458;179442457;179442456
N2AB	21258	63997;63998;63999	chr2:178577731;178577730;178577729	chr2:179442458;179442457;179442456
N2A	20331	61216;61217;61218	chr2:178577731;178577730;178577729	chr2:179442458;179442457;179442456
N2B	13834	41725;41726;41727	chr2:178577731;178577730;178577729	chr2:179442458;179442457;179442456
Novex-1	13959	42100;42101;42102	chr2:178577731;178577730;178577729	chr2:179442458;179442457;179442456
Novex-2	14026	42301;42302;42303	chr2:178577731;178577730;178577729	chr2:179442458;179442457;179442456
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-54
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.1957
• 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
C/Y	None	None	1.0	N	0.783	0.367	0.739227818891	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
C/A	0.3828	ambiguous	0.3967	ambiguous	-1.7	Destabilizing	0.998	D	0.48	neutral	None	None	None	None	N
C/D	0.7332	likely_pathogenic	0.721	pathogenic	-0.781	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
C/E	0.7021	likely_pathogenic	0.7372	pathogenic	-0.609	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
C/F	0.3698	ambiguous	0.3665	ambiguous	-1.079	Destabilizing	1.0	D	0.77	deleterious	N	0.507224445	None	None	N
C/G	0.1927	likely_benign	0.1842	benign	-2.028	Highly Destabilizing	1.0	D	0.764	deleterious	N	0.495256257	None	None	N
C/H	0.457	ambiguous	0.4542	ambiguous	-1.869	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
C/I	0.633	likely_pathogenic	0.6691	pathogenic	-0.827	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
C/K	0.4871	ambiguous	0.5204	ambiguous	-0.933	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
C/L	0.3745	ambiguous	0.4063	ambiguous	-0.827	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	N
C/M	0.5239	ambiguous	0.5503	ambiguous	0.282	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
C/N	0.3085	likely_benign	0.3006	benign	-1.334	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
C/P	0.5796	likely_pathogenic	0.6998	pathogenic	-1.095	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
C/Q	0.4434	ambiguous	0.4847	ambiguous	-1.049	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
C/R	0.2486	likely_benign	0.2734	benign	-0.947	Destabilizing	1.0	D	0.815	deleterious	N	0.472957156	None	None	N
C/S	0.3437	ambiguous	0.3305	benign	-1.782	Destabilizing	1.0	D	0.671	neutral	N	0.511280684	None	None	N
C/T	0.2944	likely_benign	0.2928	benign	-1.423	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
C/V	0.4958	ambiguous	0.5251	ambiguous	-1.095	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
C/W	0.6685	likely_pathogenic	0.6732	pathogenic	-1.203	Destabilizing	1.0	D	0.791	deleterious	N	0.496523704	None	None	N
C/Y	0.3533	ambiguous	0.3432	ambiguous	-1.124	Destabilizing	1.0	D	0.783	deleterious	N	0.516844006	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.