TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5965	18118;18119;18120	chr2:178730640;178730639;178730638	chr2:179595367;179595366;179595365
N2AB	5648	17167;17168;17169	chr2:178730640;178730639;178730638	chr2:179595367;179595366;179595365
N2A	4721	14386;14387;14388	chr2:178730640;178730639;178730638	chr2:179595367;179595366;179595365
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-43
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.161
• 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	rs752226947	-1.383	None	N	0.131	0.117	0.26547132957	gnomAD-2.1.1	5.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.09728E-04	0
Y/H	rs752226947	-1.383	None	N	0.131	0.117	0.26547132957	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.32341E-04	0	0
Y/H	rs752226947	-1.383	None	N	0.131	0.117	0.26547132957	gnomAD-4.0.0	2.60307E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.13644E-05	0	8.00743E-05

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	0.8426	likely_pathogenic	0.7422	pathogenic	-2.543	Highly Destabilizing	0.272	N	0.547	neutral	None	None	None	None	N
Y/C	0.2127	likely_benign	0.1442	benign	-1.825	Destabilizing	0.958	D	0.652	neutral	N	0.502915346	None	None	N
Y/D	0.847	likely_pathogenic	0.7356	pathogenic	-2.028	Highly Destabilizing	0.497	N	0.617	neutral	N	0.508853602	None	None	N
Y/E	0.8772	likely_pathogenic	0.782	pathogenic	-1.828	Destabilizing	0.157	N	0.567	neutral	None	None	None	None	N
Y/F	0.1478	likely_benign	0.1334	benign	-0.876	Destabilizing	0.22	N	0.514	neutral	N	0.509027891	None	None	N
Y/G	0.808	likely_pathogenic	0.7116	pathogenic	-2.966	Highly Destabilizing	0.272	N	0.605	neutral	None	None	None	None	N
Y/H	0.2635	likely_benign	0.1426	benign	-1.596	Destabilizing	None	N	0.131	neutral	N	0.504584864	None	None	N
Y/I	0.6071	likely_pathogenic	0.5065	ambiguous	-1.181	Destabilizing	0.726	D	0.585	neutral	None	None	None	None	N
Y/K	0.8326	likely_pathogenic	0.7148	pathogenic	-1.833	Destabilizing	0.567	D	0.565	neutral	None	None	None	None	N
Y/L	0.5999	likely_pathogenic	0.4923	ambiguous	-1.181	Destabilizing	0.272	N	0.515	neutral	None	None	None	None	N
Y/M	0.7213	likely_pathogenic	0.6443	pathogenic	-1.14	Destabilizing	0.968	D	0.583	neutral	None	None	None	None	N
Y/N	0.4371	ambiguous	0.2873	benign	-2.519	Highly Destabilizing	0.124	N	0.553	neutral	N	0.518804329	None	None	N
Y/P	0.9876	likely_pathogenic	0.9743	pathogenic	-1.642	Destabilizing	0.726	D	0.685	prob.neutral	None	None	None	None	N
Y/Q	0.7193	likely_pathogenic	0.5319	ambiguous	-2.22	Highly Destabilizing	0.567	D	0.587	neutral	None	None	None	None	N
Y/R	0.6668	likely_pathogenic	0.4933	ambiguous	-1.698	Destabilizing	0.567	D	0.582	neutral	None	None	None	None	N
Y/S	0.6569	likely_pathogenic	0.512	ambiguous	-3.065	Highly Destabilizing	0.22	N	0.555	neutral	N	0.506522971	None	None	N
Y/T	0.7374	likely_pathogenic	0.5912	pathogenic	-2.738	Highly Destabilizing	0.567	D	0.582	neutral	None	None	None	None	N
Y/V	0.4913	ambiguous	0.4026	ambiguous	-1.642	Destabilizing	0.431	N	0.519	neutral	None	None	None	None	N
Y/W	0.5573	ambiguous	0.4575	ambiguous	-0.249	Destabilizing	0.968	D	0.53	neutral	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.