TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17347	52264;52265;52266	chr2:178609271;178609270;178609269	chr2:179473998;179473997;179473996
N2AB	15706	47341;47342;47343	chr2:178609271;178609270;178609269	chr2:179473998;179473997;179473996
N2A	14779	44560;44561;44562	chr2:178609271;178609270;178609269	chr2:179473998;179473997;179473996
N2B	8282	25069;25070;25071	chr2:178609271;178609270;178609269	chr2:179473998;179473997;179473996
Novex-1	8407	25444;25445;25446	chr2:178609271;178609270;178609269	chr2:179473998;179473997;179473996
Novex-2	8474	25645;25646;25647	chr2:178609271;178609270;178609269	chr2:179473998;179473997;179473996
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-112
• Domain position: 97
• Structural Position: 154
• Q(SASA): 0.1019
• 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	rs1488285179	-1.818	0.667	D	0.727	0.794	0.631704462594	gnomAD-2.1.1	4.63E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1E-05	0
Y/H	rs1488285179	-1.818	0.667	D	0.727	0.794	0.631704462594	gnomAD-4.0.0	1.69485E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.00645E-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
Y/A	0.9926	likely_pathogenic	0.9932	pathogenic	-2.262	Highly Destabilizing	0.272	N	0.82	deleterious	None	None	None	None	N
Y/C	0.8685	likely_pathogenic	0.879	pathogenic	-1.673	Destabilizing	0.958	D	0.895	deleterious	D	0.597936044	None	None	N
Y/D	0.9941	likely_pathogenic	0.9944	pathogenic	-2.932	Highly Destabilizing	0.859	D	0.884	deleterious	D	0.597936044	None	None	N
Y/E	0.9973	likely_pathogenic	0.9976	pathogenic	-2.686	Highly Destabilizing	0.726	D	0.853	deleterious	None	None	None	None	N
Y/F	0.0702	likely_benign	0.0812	benign	-0.744	Destabilizing	None	N	0.393	neutral	D	0.556616165	None	None	N
Y/G	0.9866	likely_pathogenic	0.9873	pathogenic	-2.717	Highly Destabilizing	0.726	D	0.843	deleterious	None	None	None	None	N
Y/H	0.9157	likely_pathogenic	0.9186	pathogenic	-1.971	Destabilizing	0.667	D	0.727	prob.delet.	D	0.59773424	None	None	N
Y/I	0.8785	likely_pathogenic	0.8901	pathogenic	-0.759	Destabilizing	0.157	N	0.765	deleterious	None	None	None	None	N
Y/K	0.9957	likely_pathogenic	0.9963	pathogenic	-1.93	Destabilizing	0.726	D	0.856	deleterious	None	None	None	None	N
Y/L	0.8144	likely_pathogenic	0.8142	pathogenic	-0.759	Destabilizing	0.072	N	0.731	prob.delet.	None	None	None	None	N
Y/M	0.9417	likely_pathogenic	0.9515	pathogenic	-0.826	Destabilizing	0.726	D	0.814	deleterious	None	None	None	None	N
Y/N	0.9773	likely_pathogenic	0.9776	pathogenic	-2.876	Highly Destabilizing	0.859	D	0.879	deleterious	D	0.597936044	None	None	N
Y/P	0.9967	likely_pathogenic	0.9969	pathogenic	-1.275	Destabilizing	0.89	D	0.895	deleterious	None	None	None	None	N
Y/Q	0.9942	likely_pathogenic	0.995	pathogenic	-2.425	Highly Destabilizing	0.89	D	0.789	deleterious	None	None	None	None	N
Y/R	0.9867	likely_pathogenic	0.988	pathogenic	-2.179	Highly Destabilizing	0.726	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9824	likely_pathogenic	0.9832	pathogenic	-3.196	Highly Destabilizing	0.667	D	0.82	deleterious	D	0.597936044	None	None	N
Y/T	0.9906	likely_pathogenic	0.9917	pathogenic	-2.801	Highly Destabilizing	0.726	D	0.819	deleterious	None	None	None	None	N
Y/V	0.8744	likely_pathogenic	0.8849	pathogenic	-1.275	Destabilizing	0.157	N	0.75	deleterious	None	None	None	None	N
Y/W	0.6011	likely_pathogenic	0.6262	pathogenic	-0.134	Destabilizing	0.726	D	0.765	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.