TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1566	4921;4922;4923	chr2:178777267;178777266;178777265	chr2:179641994;179641993;179641992
N2AB	1566	4921;4922;4923	chr2:178777267;178777266;178777265	chr2:179641994;179641993;179641992
N2A	1566	4921;4922;4923	chr2:178777267;178777266;178777265	chr2:179641994;179641993;179641992
N2B	1520	4783;4784;4785	chr2:178777267;178777266;178777265	chr2:179641994;179641993;179641992
Novex-1	1520	4783;4784;4785	chr2:178777267;178777266;178777265	chr2:179641994;179641993;179641992
Novex-2	1520	4783;4784;4785	chr2:178777267;178777266;178777265	chr2:179641994;179641993;179641992
Novex-3	1566	4921;4922;4923	chr2:178777267;178777266;178777265	chr2:179641994;179641993;179641992

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-7
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5959
• 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/D	None	None	0.425	N	0.261	0.291	0.302793454619	gnomAD-4.0.0	1.59081E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85682E-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	0.2578	likely_benign	0.2026	benign	-0.385	Destabilizing	0.176	N	0.257	neutral	None	None	None	None	N
N/C	0.3594	ambiguous	0.2673	benign	0.307	Stabilizing	0.995	D	0.33	neutral	None	None	None	None	N
N/D	0.2397	likely_benign	0.1892	benign	0.02	Stabilizing	0.425	N	0.261	neutral	N	0.50038977	None	None	N
N/E	0.587	likely_pathogenic	0.4684	ambiguous	0.008	Stabilizing	0.495	N	0.229	neutral	None	None	None	None	N
N/F	0.5853	likely_pathogenic	0.4963	ambiguous	-0.613	Destabilizing	0.981	D	0.361	neutral	None	None	None	None	N
N/G	0.3503	ambiguous	0.2884	benign	-0.6	Destabilizing	0.329	N	0.272	neutral	None	None	None	None	N
N/H	0.1267	likely_benign	0.1083	benign	-0.593	Destabilizing	0.975	D	0.33	neutral	N	0.509452657	None	None	N
N/I	0.2253	likely_benign	0.1828	benign	0.101	Stabilizing	0.642	D	0.42	neutral	N	0.475339125	None	None	N
N/K	0.4874	ambiguous	0.3702	ambiguous	0.012	Stabilizing	0.425	N	0.229	neutral	N	0.477865236	None	None	N
N/L	0.2568	likely_benign	0.2085	benign	0.101	Stabilizing	0.495	N	0.353	neutral	None	None	None	None	N
N/M	0.3495	ambiguous	0.2894	benign	0.436	Stabilizing	0.981	D	0.329	neutral	None	None	None	None	N
N/P	0.6829	likely_pathogenic	0.569	pathogenic	-0.033	Destabilizing	0.828	D	0.396	neutral	None	None	None	None	N
N/Q	0.4284	ambiguous	0.3333	benign	-0.458	Destabilizing	0.828	D	0.287	neutral	None	None	None	None	N
N/R	0.5121	ambiguous	0.3936	ambiguous	0.049	Stabilizing	0.704	D	0.214	neutral	None	None	None	None	N
N/S	0.0828	likely_benign	0.0773	benign	-0.262	Destabilizing	0.003	N	0.107	neutral	N	0.387577125	None	None	N
N/T	0.1187	likely_benign	0.1005	benign	-0.119	Destabilizing	0.003	N	0.101	neutral	N	0.350094916	None	None	N
N/V	0.233	likely_benign	0.1874	benign	-0.033	Destabilizing	0.704	D	0.381	neutral	None	None	None	None	N
N/W	0.8561	likely_pathogenic	0.7826	pathogenic	-0.547	Destabilizing	0.995	D	0.357	neutral	None	None	None	None	N
N/Y	0.2469	likely_benign	0.2016	benign	-0.301	Destabilizing	0.975	D	0.337	neutral	N	0.475835001	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.