TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19204	57835;57836;57837	chr2:178595744;178595743;178595742	chr2:179460471;179460470;179460469
N2AB	17563	52912;52913;52914	chr2:178595744;178595743;178595742	chr2:179460471;179460470;179460469
N2A	16636	50131;50132;50133	chr2:178595744;178595743;178595742	chr2:179460471;179460470;179460469
N2B	10139	30640;30641;30642	chr2:178595744;178595743;178595742	chr2:179460471;179460470;179460469
Novex-1	10264	31015;31016;31017	chr2:178595744;178595743;178595742	chr2:179460471;179460470;179460469
Novex-2	10331	31216;31217;31218	chr2:178595744;178595743;178595742	chr2:179460471;179460470;179460469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-27
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.2087
• 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
T/P	None	None	0.997	N	0.777	0.448	0.512021964565	gnomAD-4.0.0	6.8612E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00812E-07	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
T/A	0.1174	likely_benign	0.1095	benign	-0.814	Destabilizing	0.898	D	0.542	neutral	N	0.470092996	None	None	N
T/C	0.4653	ambiguous	0.4192	ambiguous	-0.545	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/D	0.5392	ambiguous	0.5185	ambiguous	-1.838	Destabilizing	0.995	D	0.682	prob.neutral	None	None	None	None	N
T/E	0.4536	ambiguous	0.4297	ambiguous	-1.584	Destabilizing	0.995	D	0.671	neutral	None	None	None	None	N
T/F	0.3196	likely_benign	0.2927	benign	-0.422	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
T/G	0.3504	ambiguous	0.3151	benign	-1.236	Destabilizing	0.966	D	0.587	neutral	None	None	None	None	N
T/H	0.3154	likely_benign	0.2935	benign	-1.408	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
T/I	0.2149	likely_benign	0.2115	benign	0.32	Stabilizing	0.997	D	0.768	deleterious	N	0.518174944	None	None	N
T/K	0.432	ambiguous	0.3994	ambiguous	-0.327	Destabilizing	0.993	D	0.677	prob.neutral	N	0.466783332	None	None	N
T/L	0.1294	likely_benign	0.1247	benign	0.32	Stabilizing	0.983	D	0.575	neutral	None	None	None	None	N
T/M	0.1057	likely_benign	0.1045	benign	0.037	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
T/N	0.1456	likely_benign	0.1371	benign	-1.246	Destabilizing	0.995	D	0.697	prob.neutral	None	None	None	None	N
T/P	0.7115	likely_pathogenic	0.708	pathogenic	-0.03	Destabilizing	0.997	D	0.777	deleterious	N	0.492755177	None	None	N
T/Q	0.3008	likely_benign	0.2848	benign	-0.816	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
T/R	0.3442	ambiguous	0.3237	benign	-0.79	Destabilizing	0.993	D	0.769	deleterious	N	0.467071334	None	None	N
T/S	0.1128	likely_benign	0.1032	benign	-1.339	Destabilizing	0.362	N	0.439	neutral	N	0.400150121	None	None	N
T/V	0.1769	likely_benign	0.1713	benign	-0.03	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
T/W	0.7007	likely_pathogenic	0.6483	pathogenic	-0.862	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
T/Y	0.3568	ambiguous	0.3146	benign	-0.36	Destabilizing	0.999	D	0.859	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.