TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13809	41650;41651;41652	chr2:178636146;178636145;178636144	chr2:179500873;179500872;179500871
N2AB	12168	36727;36728;36729	chr2:178636146;178636145;178636144	chr2:179500873;179500872;179500871
N2A	11241	33946;33947;33948	chr2:178636146;178636145;178636144	chr2:179500873;179500872;179500871
N2B	4744	14455;14456;14457	chr2:178636146;178636145;178636144	chr2:179500873;179500872;179500871
Novex-1	4869	14830;14831;14832	chr2:178636146;178636145;178636144	chr2:179500873;179500872;179500871
Novex-2	4936	15031;15032;15033	chr2:178636146;178636145;178636144	chr2:179500873;179500872;179500871
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: Ig-88
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.7528
• 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
D/N	rs761516226	0.001	0.059	N	0.271	0.083	0.101711395817	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	8.9E-06	0
D/N	rs761516226	0.001	0.059	N	0.271	0.083	0.101711395817	gnomAD-4.0.0	3.18579E-06	None	None	None	None	I	None	0	2.2877E-05	None	0	0	None	0	0	2.86059E-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	0.3422	ambiguous	0.3405	ambiguous	-0.079	Destabilizing	0.811	D	0.584	neutral	N	0.332452957	None	None	I
D/C	0.9109	likely_pathogenic	0.9008	pathogenic	-0.024	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	I
D/E	0.3229	likely_benign	0.3141	benign	-0.351	Destabilizing	0.226	N	0.225	neutral	N	0.343702297	None	None	I
D/F	0.8739	likely_pathogenic	0.8707	pathogenic	0.081	Stabilizing	0.996	D	0.789	deleterious	None	None	None	None	I
D/G	0.3787	ambiguous	0.357	ambiguous	-0.293	Destabilizing	0.811	D	0.593	neutral	N	0.361285048	None	None	I
D/H	0.6271	likely_pathogenic	0.5943	pathogenic	0.312	Stabilizing	0.996	D	0.682	prob.neutral	N	0.331061515	None	None	I
D/I	0.7149	likely_pathogenic	0.7206	pathogenic	0.435	Stabilizing	0.988	D	0.821	deleterious	None	None	None	None	I
D/K	0.7135	likely_pathogenic	0.6891	pathogenic	0.424	Stabilizing	0.919	D	0.629	neutral	None	None	None	None	I
D/L	0.6971	likely_pathogenic	0.6976	pathogenic	0.435	Stabilizing	0.976	D	0.765	deleterious	None	None	None	None	I
D/M	0.8844	likely_pathogenic	0.8842	pathogenic	0.377	Stabilizing	0.999	D	0.792	deleterious	None	None	None	None	I
D/N	0.1861	likely_benign	0.1744	benign	0.008	Stabilizing	0.059	N	0.271	neutral	N	0.338468588	None	None	I
D/P	0.7355	likely_pathogenic	0.753	pathogenic	0.287	Stabilizing	0.988	D	0.662	prob.neutral	None	None	None	None	I
D/Q	0.6892	likely_pathogenic	0.6625	pathogenic	0.055	Stabilizing	0.976	D	0.521	neutral	None	None	None	None	I
D/R	0.7661	likely_pathogenic	0.7429	pathogenic	0.643	Stabilizing	0.976	D	0.802	deleterious	None	None	None	None	I
D/S	0.2783	likely_benign	0.2626	benign	-0.072	Destabilizing	0.261	N	0.287	neutral	None	None	None	None	I
D/T	0.507	ambiguous	0.4998	ambiguous	0.098	Stabilizing	0.851	D	0.631	neutral	None	None	None	None	I
D/V	0.4825	ambiguous	0.48	ambiguous	0.287	Stabilizing	0.968	D	0.779	deleterious	N	0.329968144	None	None	I
D/W	0.9776	likely_pathogenic	0.9779	pathogenic	0.211	Stabilizing	0.999	D	0.735	deleterious	None	None	None	None	I
D/Y	0.523	ambiguous	0.4944	ambiguous	0.331	Stabilizing	0.995	D	0.786	deleterious	N	0.316589176	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.