TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24738	74437;74438;74439	chr2:178571920;178571919;178571918	chr2:179436647;179436646;179436645
N2AB	23097	69514;69515;69516	chr2:178571920;178571919;178571918	chr2:179436647;179436646;179436645
N2A	22170	66733;66734;66735	chr2:178571920;178571919;178571918	chr2:179436647;179436646;179436645
N2B	15673	47242;47243;47244	chr2:178571920;178571919;178571918	chr2:179436647;179436646;179436645
Novex-1	15798	47617;47618;47619	chr2:178571920;178571919;178571918	chr2:179436647;179436646;179436645
Novex-2	15865	47818;47819;47820	chr2:178571920;178571919;178571918	chr2:179436647;179436646;179436645
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-133
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.197
• 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
P/L	None	None	0.994	N	0.765	0.455	0.837415841873	gnomAD-4.0.0	1.59246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86005E-06	0	0
P/R	None	None	0.994	N	0.802	0.456	0.709956786332	gnomAD-4.0.0	1.59246E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88374E-05	0	0	0	0
P/T	None	None	0.994	N	0.795	0.393	0.617781757779	gnomAD-4.0.0	1.59252E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88395E-05	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
P/A	0.261	likely_benign	0.2707	benign	-1.689	Destabilizing	0.919	D	0.574	neutral	D	0.530285811	None	None	N
P/C	0.8321	likely_pathogenic	0.8459	pathogenic	-1.095	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/D	0.8616	likely_pathogenic	0.8788	pathogenic	-1.692	Destabilizing	0.991	D	0.795	deleterious	None	None	None	None	N
P/E	0.745	likely_pathogenic	0.7716	pathogenic	-1.609	Destabilizing	0.995	D	0.796	deleterious	None	None	None	None	N
P/F	0.8961	likely_pathogenic	0.8919	pathogenic	-1.173	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/G	0.7081	likely_pathogenic	0.7226	pathogenic	-2.096	Highly Destabilizing	0.086	N	0.499	neutral	None	None	None	None	N
P/H	0.5544	ambiguous	0.5916	pathogenic	-1.739	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/I	0.7313	likely_pathogenic	0.7268	pathogenic	-0.629	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
P/K	0.7138	likely_pathogenic	0.7491	pathogenic	-1.363	Destabilizing	0.991	D	0.795	deleterious	None	None	None	None	N
P/L	0.3761	ambiguous	0.3647	ambiguous	-0.629	Destabilizing	0.994	D	0.765	deleterious	N	0.498770609	None	None	N
P/M	0.7396	likely_pathogenic	0.7385	pathogenic	-0.475	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/N	0.7261	likely_pathogenic	0.757	pathogenic	-1.321	Destabilizing	0.991	D	0.774	deleterious	None	None	None	None	N
P/Q	0.4993	ambiguous	0.5241	ambiguous	-1.371	Destabilizing	0.998	D	0.815	deleterious	N	0.498704475	None	None	N
P/R	0.5168	ambiguous	0.5507	ambiguous	-0.974	Destabilizing	0.994	D	0.802	deleterious	N	0.481854441	None	None	N
P/S	0.4082	ambiguous	0.4388	ambiguous	-1.91	Destabilizing	0.988	D	0.735	prob.delet.	N	0.481854441	None	None	N
P/T	0.3521	ambiguous	0.3769	ambiguous	-1.707	Destabilizing	0.994	D	0.795	deleterious	N	0.481623724	None	None	N
P/V	0.5865	likely_pathogenic	0.5807	pathogenic	-0.949	Destabilizing	0.995	D	0.766	deleterious	None	None	None	None	N
P/W	0.9472	likely_pathogenic	0.9505	pathogenic	-1.522	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/Y	0.8464	likely_pathogenic	0.8572	pathogenic	-1.169	Destabilizing	1.0	D	0.802	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.