TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30690	92293;92294;92295	chr2:178549654;178549653;178549652	chr2:179414381;179414380;179414379
N2AB	29049	87370;87371;87372	chr2:178549654;178549653;178549652	chr2:179414381;179414380;179414379
N2A	28122	84589;84590;84591	chr2:178549654;178549653;178549652	chr2:179414381;179414380;179414379
N2B	21625	65098;65099;65100	chr2:178549654;178549653;178549652	chr2:179414381;179414380;179414379
Novex-1	21750	65473;65474;65475	chr2:178549654;178549653;178549652	chr2:179414381;179414380;179414379
Novex-2	21817	65674;65675;65676	chr2:178549654;178549653;178549652	chr2:179414381;179414380;179414379
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-111
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0974
• 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
Y/H	None	None	1.0	D	0.844	0.895	0.743349697248	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-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
Y/A	0.9993	likely_pathogenic	0.9993	pathogenic	-3.633	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/C	0.9939	likely_pathogenic	0.9943	pathogenic	-2.181	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.688258762	None	None	N
Y/D	0.9981	likely_pathogenic	0.9978	pathogenic	-3.906	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.688258762	None	None	N
Y/E	0.9995	likely_pathogenic	0.9995	pathogenic	-3.723	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/F	0.7111	likely_pathogenic	0.7224	pathogenic	-1.434	Destabilizing	0.999	D	0.762	deleterious	D	0.641170416	None	None	N
Y/G	0.9958	likely_pathogenic	0.9959	pathogenic	-4.008	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/H	0.9968	likely_pathogenic	0.9966	pathogenic	-2.485	Highly Destabilizing	1.0	D	0.844	deleterious	D	0.688258762	None	None	N
Y/I	0.9888	likely_pathogenic	0.9897	pathogenic	-2.36	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/K	0.9995	likely_pathogenic	0.9994	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/L	0.9779	likely_pathogenic	0.9773	pathogenic	-2.36	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
Y/M	0.9951	likely_pathogenic	0.9952	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/N	0.9884	likely_pathogenic	0.9893	pathogenic	-3.321	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.688056957	None	None	N
Y/P	0.9997	likely_pathogenic	0.9996	pathogenic	-2.802	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/Q	0.9996	likely_pathogenic	0.9995	pathogenic	-3.14	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/R	0.9988	likely_pathogenic	0.9987	pathogenic	-2.182	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/S	0.9968	likely_pathogenic	0.9967	pathogenic	-3.647	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.688258762	None	None	N
Y/T	0.9987	likely_pathogenic	0.9987	pathogenic	-3.363	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9821	likely_pathogenic	0.9832	pathogenic	-2.802	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/W	0.9719	likely_pathogenic	0.971	pathogenic	-0.743	Destabilizing	1.0	D	0.821	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.