TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14538	43837;43838;43839	chr2:178632282;178632281;178632280	chr2:179497009;179497008;179497007
N2AB	12897	38914;38915;38916	chr2:178632282;178632281;178632280	chr2:179497009;179497008;179497007
N2A	11970	36133;36134;36135	chr2:178632282;178632281;178632280	chr2:179497009;179497008;179497007
N2B	5473	16642;16643;16644	chr2:178632282;178632281;178632280	chr2:179497009;179497008;179497007
Novex-1	5598	17017;17018;17019	chr2:178632282;178632281;178632280	chr2:179497009;179497008;179497007
Novex-2	5665	17218;17219;17220	chr2:178632282;178632281;178632280	chr2:179497009;179497008;179497007
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-96
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.3502
• 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/A	None	None	0.78	N	0.409	0.203	0.311387274539	gnomAD-4.0.0	4.80183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87176E-06	0	6.07128E-05
T/I	None	None	0.984	N	0.419	0.451	0.488125499135	gnomAD-4.0.0	6.8594E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00836E-07	0	0
T/N	None	None	0.995	N	0.398	0.341	0.434606191737	gnomAD-4.0.0	6.8594E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00836E-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	0.0876	likely_benign	0.0828	benign	-0.32	Destabilizing	0.78	D	0.409	neutral	N	0.493702042	None	None	N
T/C	0.5589	ambiguous	0.5279	ambiguous	-0.231	Destabilizing	0.999	D	0.46	neutral	None	None	None	None	N
T/D	0.4069	ambiguous	0.3786	ambiguous	0.101	Stabilizing	0.959	D	0.409	neutral	None	None	None	None	N
T/E	0.3105	likely_benign	0.2835	benign	0.019	Stabilizing	0.919	D	0.413	neutral	None	None	None	None	N
T/F	0.3195	likely_benign	0.2969	benign	-0.862	Destabilizing	0.996	D	0.52	neutral	None	None	None	None	N
T/G	0.2912	likely_benign	0.2663	benign	-0.436	Destabilizing	0.959	D	0.482	neutral	None	None	None	None	N
T/H	0.285	likely_benign	0.2573	benign	-0.748	Destabilizing	0.999	D	0.514	neutral	None	None	None	None	N
T/I	0.2207	likely_benign	0.2229	benign	-0.135	Destabilizing	0.984	D	0.419	neutral	N	0.512068058	None	None	N
T/K	0.1944	likely_benign	0.1798	benign	-0.357	Destabilizing	0.919	D	0.41	neutral	None	None	None	None	N
T/L	0.1257	likely_benign	0.1297	benign	-0.135	Destabilizing	0.959	D	0.396	neutral	None	None	None	None	N
T/M	0.1134	likely_benign	0.1124	benign	0.014	Stabilizing	0.999	D	0.441	neutral	None	None	None	None	N
T/N	0.1491	likely_benign	0.1395	benign	-0.12	Destabilizing	0.995	D	0.398	neutral	N	0.508330543	None	None	N
T/P	0.0841	likely_benign	0.0826	benign	-0.169	Destabilizing	0.004	N	0.179	neutral	N	0.389350895	None	None	N
T/Q	0.2461	likely_benign	0.2238	benign	-0.347	Destabilizing	0.996	D	0.429	neutral	None	None	None	None	N
T/R	0.1551	likely_benign	0.1428	benign	-0.091	Destabilizing	0.988	D	0.422	neutral	None	None	None	None	N
T/S	0.1421	likely_benign	0.1323	benign	-0.302	Destabilizing	0.896	D	0.46	neutral	N	0.501552749	None	None	N
T/V	0.1808	likely_benign	0.1798	benign	-0.169	Destabilizing	0.959	D	0.392	neutral	None	None	None	None	N
T/W	0.6834	likely_pathogenic	0.6502	pathogenic	-0.893	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
T/Y	0.3596	ambiguous	0.3295	benign	-0.598	Destabilizing	0.996	D	0.519	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.