TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30918	92977;92978;92979	chr2:178548874;178548873;178548872	chr2:179413601;179413600;179413599
N2AB	29277	88054;88055;88056	chr2:178548874;178548873;178548872	chr2:179413601;179413600;179413599
N2A	28350	85273;85274;85275	chr2:178548874;178548873;178548872	chr2:179413601;179413600;179413599
N2B	21853	65782;65783;65784	chr2:178548874;178548873;178548872	chr2:179413601;179413600;179413599
Novex-1	21978	66157;66158;66159	chr2:178548874;178548873;178548872	chr2:179413601;179413600;179413599
Novex-2	22045	66358;66359;66360	chr2:178548874;178548873;178548872	chr2:179413601;179413600;179413599
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-113
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.9868
• 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
D/Y	rs781654770	0.12	1.0	N	0.831	0.58	0.73377832567	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
D/Y	rs781654770	0.12	1.0	N	0.831	0.58	0.73377832567	gnomAD-4.0.0	6.1582E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09497E-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
D/A	0.7565	likely_pathogenic	0.7302	pathogenic	0.05	Stabilizing	1.0	D	0.746	deleterious	N	0.486993607	None	None	N
D/C	0.9523	likely_pathogenic	0.9454	pathogenic	0.03	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
D/E	0.3372	likely_benign	0.3018	benign	-0.214	Destabilizing	0.999	D	0.464	neutral	N	0.412015845	None	None	N
D/F	0.9724	likely_pathogenic	0.9676	pathogenic	-0.042	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/G	0.7769	likely_pathogenic	0.7502	pathogenic	-0.062	Destabilizing	1.0	D	0.797	deleterious	D	0.529131018	None	None	N
D/H	0.8684	likely_pathogenic	0.8515	pathogenic	0.412	Stabilizing	1.0	D	0.898	deleterious	N	0.487855149	None	None	N
D/I	0.9449	likely_pathogenic	0.9388	pathogenic	0.278	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
D/K	0.9388	likely_pathogenic	0.9301	pathogenic	0.565	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/L	0.9067	likely_pathogenic	0.8959	pathogenic	0.278	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
D/M	0.9743	likely_pathogenic	0.972	pathogenic	0.168	Stabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
D/N	0.4567	ambiguous	0.4468	ambiguous	0.325	Stabilizing	1.0	D	0.791	deleterious	N	0.517836589	None	None	N
D/P	0.9109	likely_pathogenic	0.889	pathogenic	0.221	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
D/Q	0.8545	likely_pathogenic	0.8377	pathogenic	0.334	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
D/R	0.9386	likely_pathogenic	0.9311	pathogenic	0.687	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
D/S	0.5917	likely_pathogenic	0.5662	pathogenic	0.248	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
D/T	0.8691	likely_pathogenic	0.8564	pathogenic	0.344	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
D/V	0.8529	likely_pathogenic	0.8367	pathogenic	0.221	Stabilizing	1.0	D	0.792	deleterious	N	0.499718434	None	None	N
D/W	0.9922	likely_pathogenic	0.9913	pathogenic	-0.005	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
D/Y	0.8278	likely_pathogenic	0.8042	pathogenic	0.181	Stabilizing	1.0	D	0.831	deleterious	N	0.500225413	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.