TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13936	42031;42032;42033	chr2:178635518;178635517;178635516	chr2:179500245;179500244;179500243
N2AB	12295	37108;37109;37110	chr2:178635518;178635517;178635516	chr2:179500245;179500244;179500243
N2A	11368	34327;34328;34329	chr2:178635518;178635517;178635516	chr2:179500245;179500244;179500243
N2B	4871	14836;14837;14838	chr2:178635518;178635517;178635516	chr2:179500245;179500244;179500243
Novex-1	4996	15211;15212;15213	chr2:178635518;178635517;178635516	chr2:179500245;179500244;179500243
Novex-2	5063	15412;15413;15414	chr2:178635518;178635517;178635516	chr2:179500245;179500244;179500243
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-89
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.4669
• 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
N/H	None	None	1.0	D	0.567	0.346	0.223847106136	gnomAD-4.0.0	2.07122E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71602E-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
N/A	0.6753	likely_pathogenic	0.7099	pathogenic	-0.481	Destabilizing	0.993	D	0.443	neutral	None	None	None	None	N
N/C	0.8019	likely_pathogenic	0.8595	pathogenic	0.399	Stabilizing	1.0	D	0.587	neutral	None	None	None	None	N
N/D	0.2857	likely_benign	0.3107	benign	-0.303	Destabilizing	0.996	D	0.415	neutral	D	0.532252729	None	None	N
N/E	0.7514	likely_pathogenic	0.7472	pathogenic	-0.307	Destabilizing	0.993	D	0.437	neutral	None	None	None	None	N
N/F	0.8785	likely_pathogenic	0.8887	pathogenic	-0.669	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
N/G	0.5766	likely_pathogenic	0.632	pathogenic	-0.714	Destabilizing	0.997	D	0.4	neutral	None	None	None	None	N
N/H	0.336	likely_benign	0.373	ambiguous	-0.743	Destabilizing	1.0	D	0.567	neutral	D	0.540677393	None	None	N
N/I	0.8549	likely_pathogenic	0.8601	pathogenic	0.061	Stabilizing	1.0	D	0.651	prob.neutral	D	0.542703199	None	None	N
N/K	0.7988	likely_pathogenic	0.7893	pathogenic	-0.061	Destabilizing	0.603	D	0.343	neutral	N	0.45153498	None	None	N
N/L	0.7486	likely_pathogenic	0.7622	pathogenic	0.061	Stabilizing	0.999	D	0.573	neutral	None	None	None	None	N
N/M	0.7531	likely_pathogenic	0.7783	pathogenic	0.644	Stabilizing	1.0	D	0.528	neutral	None	None	None	None	N
N/P	0.9824	likely_pathogenic	0.9822	pathogenic	-0.091	Destabilizing	1.0	D	0.523	neutral	None	None	None	None	N
N/Q	0.7213	likely_pathogenic	0.7377	pathogenic	-0.593	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
N/R	0.8445	likely_pathogenic	0.8455	pathogenic	0.021	Stabilizing	0.996	D	0.527	neutral	None	None	None	None	N
N/S	0.2751	likely_benign	0.3256	benign	-0.35	Destabilizing	0.991	D	0.397	neutral	D	0.530658889	None	None	N
N/T	0.5615	ambiguous	0.5848	pathogenic	-0.201	Destabilizing	0.996	D	0.484	neutral	D	0.540181439	None	None	N
N/V	0.8091	likely_pathogenic	0.824	pathogenic	-0.091	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
N/W	0.9603	likely_pathogenic	0.97	pathogenic	-0.572	Destabilizing	1.0	D	0.513	neutral	None	None	None	None	N
N/Y	0.3871	ambiguous	0.4008	ambiguous	-0.339	Destabilizing	1.0	D	0.559	neutral	D	0.541947881	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.