TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19299	58120;58121;58122	chr2:178594599;178594598;178594597	chr2:179459326;179459325;179459324
N2AB	17658	53197;53198;53199	chr2:178594599;178594598;178594597	chr2:179459326;179459325;179459324
N2A	16731	50416;50417;50418	chr2:178594599;178594598;178594597	chr2:179459326;179459325;179459324
N2B	10234	30925;30926;30927	chr2:178594599;178594598;178594597	chr2:179459326;179459325;179459324
Novex-1	10359	31300;31301;31302	chr2:178594599;178594598;178594597	chr2:179459326;179459325;179459324
Novex-2	10426	31501;31502;31503	chr2:178594599;178594598;178594597	chr2:179459326;179459325;179459324
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: Fn3-28
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4983
• 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	rs768931487	-0.861	0.295	N	0.39	0.107	0.0846915920261	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.57E-05	None	0	0	0
N/H	rs768931487	-0.861	0.295	N	0.39	0.107	0.0846915920261	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
N/H	rs768931487	-0.861	0.295	N	0.39	0.107	0.0846915920261	gnomAD-4.0.0	5.13313E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.37577E-05	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	0.219	likely_benign	0.1936	benign	-0.673	Destabilizing	0.016	N	0.326	neutral	None	None	None	None	N
N/C	0.3704	ambiguous	0.3081	benign	0.154	Stabilizing	0.864	D	0.361	neutral	None	None	None	None	N
N/D	0.0633	likely_benign	0.0752	benign	-0.613	Destabilizing	None	N	0.073	neutral	N	0.379433706	None	None	N
N/E	0.1913	likely_benign	0.2156	benign	-0.592	Destabilizing	None	N	0.099	neutral	None	None	None	None	N
N/F	0.5848	likely_pathogenic	0.5331	ambiguous	-0.753	Destabilizing	0.356	N	0.377	neutral	None	None	None	None	N
N/G	0.2731	likely_benign	0.242	benign	-0.932	Destabilizing	0.016	N	0.292	neutral	None	None	None	None	N
N/H	0.1393	likely_benign	0.1442	benign	-0.857	Destabilizing	0.295	N	0.39	neutral	N	0.478309834	None	None	N
N/I	0.4273	ambiguous	0.3969	ambiguous	-0.049	Destabilizing	0.171	N	0.429	neutral	N	0.477284268	None	None	N
N/K	0.2921	likely_benign	0.3162	benign	-0.159	Destabilizing	0.012	N	0.24	neutral	N	0.490988343	None	None	N
N/L	0.3422	ambiguous	0.3159	benign	-0.049	Destabilizing	0.072	N	0.44	neutral	None	None	None	None	N
N/M	0.3564	ambiguous	0.322	benign	0.57	Stabilizing	0.864	D	0.347	neutral	None	None	None	None	N
N/P	0.9305	likely_pathogenic	0.9248	pathogenic	-0.229	Destabilizing	0.136	N	0.417	neutral	None	None	None	None	N
N/Q	0.2746	likely_benign	0.286	benign	-0.86	Destabilizing	0.038	N	0.387	neutral	None	None	None	None	N
N/R	0.3717	ambiguous	0.3888	ambiguous	-0.037	Destabilizing	0.038	N	0.381	neutral	None	None	None	None	N
N/S	0.0883	likely_benign	0.0759	benign	-0.611	Destabilizing	None	N	0.099	neutral	N	0.426070073	None	None	N
N/T	0.0982	likely_benign	0.0888	benign	-0.427	Destabilizing	0.001	N	0.125	neutral	N	0.416485011	None	None	N
N/V	0.3585	ambiguous	0.3487	ambiguous	-0.229	Destabilizing	0.072	N	0.449	neutral	None	None	None	None	N
N/W	0.81	likely_pathogenic	0.7701	pathogenic	-0.57	Destabilizing	0.864	D	0.472	neutral	None	None	None	None	N
N/Y	0.1938	likely_benign	0.1887	benign	-0.347	Destabilizing	0.56	D	0.365	neutral	N	0.468890477	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.