TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30759	92500;92501;92502	chr2:178549351;178549350;178549349	chr2:179414078;179414077;179414076
N2AB	29118	87577;87578;87579	chr2:178549351;178549350;178549349	chr2:179414078;179414077;179414076
N2A	28191	84796;84797;84798	chr2:178549351;178549350;178549349	chr2:179414078;179414077;179414076
N2B	21694	65305;65306;65307	chr2:178549351;178549350;178549349	chr2:179414078;179414077;179414076
Novex-1	21819	65680;65681;65682	chr2:178549351;178549350;178549349	chr2:179414078;179414077;179414076
Novex-2	21886	65881;65882;65883	chr2:178549351;178549350;178549349	chr2:179414078;179414077;179414076
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-112
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.2006
• 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
R/K	rs769687279	-1.133	0.997	N	0.46	0.33	0.418344901717	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
R/K	rs769687279	-1.133	0.997	N	0.46	0.33	0.418344901717	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	0	None	0	2.773E-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
R/A	0.9877	likely_pathogenic	0.9853	pathogenic	-2.103	Highly Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
R/C	0.7241	likely_pathogenic	0.6708	pathogenic	-2.026	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
R/D	0.9985	likely_pathogenic	0.9978	pathogenic	-1.11	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
R/E	0.9761	likely_pathogenic	0.9687	pathogenic	-0.888	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	N
R/F	0.987	likely_pathogenic	0.9831	pathogenic	-1.334	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
R/G	0.9758	likely_pathogenic	0.9687	pathogenic	-2.461	Highly Destabilizing	1.0	D	0.781	deleterious	N	0.51424002	None	None	N
R/H	0.5009	ambiguous	0.4099	ambiguous	-2.208	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/I	0.9767	likely_pathogenic	0.9715	pathogenic	-1.059	Destabilizing	1.0	D	0.881	deleterious	D	0.529128271	None	None	N
R/K	0.2994	likely_benign	0.2686	benign	-1.421	Destabilizing	0.997	D	0.46	neutral	N	0.475786817	None	None	N
R/L	0.9197	likely_pathogenic	0.9014	pathogenic	-1.059	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
R/M	0.9509	likely_pathogenic	0.9363	pathogenic	-1.475	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
R/N	0.9934	likely_pathogenic	0.9905	pathogenic	-1.469	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
R/P	0.9991	likely_pathogenic	0.9989	pathogenic	-1.396	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
R/Q	0.4799	ambiguous	0.4174	ambiguous	-1.346	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
R/S	0.9944	likely_pathogenic	0.9929	pathogenic	-2.403	Highly Destabilizing	1.0	D	0.786	deleterious	N	0.492600138	None	None	N
R/T	0.9886	likely_pathogenic	0.9853	pathogenic	-1.957	Destabilizing	1.0	D	0.774	deleterious	D	0.525089346	None	None	N
R/V	0.9818	likely_pathogenic	0.9773	pathogenic	-1.396	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
R/W	0.8194	likely_pathogenic	0.7599	pathogenic	-0.821	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
R/Y	0.9549	likely_pathogenic	0.9395	pathogenic	-0.688	Destabilizing	1.0	D	0.881	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.