TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29984	90175;90176;90177	chr2:178552950;178552949;178552948	chr2:179417677;179417676;179417675
N2AB	28343	85252;85253;85254	chr2:178552950;178552949;178552948	chr2:179417677;179417676;179417675
N2A	27416	82471;82472;82473	chr2:178552950;178552949;178552948	chr2:179417677;179417676;179417675
N2B	20919	62980;62981;62982	chr2:178552950;178552949;178552948	chr2:179417677;179417676;179417675
Novex-1	21044	63355;63356;63357	chr2:178552950;178552949;178552948	chr2:179417677;179417676;179417675
Novex-2	21111	63556;63557;63558	chr2:178552950;178552949;178552948	chr2:179417677;179417676;179417675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-106
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.132
• 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
S/T	rs1306828364	None	None	N	0.165	0.063	0.152612264143	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/T	rs1306828364	None	None	N	0.165	0.063	0.152612264143	gnomAD-4.0.0	6.57497E-06	None	None	None	None	N	None	2.41429E-05	0	None	0	0	None	0	0	0	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
S/A	0.106	likely_benign	0.0986	benign	-0.531	Destabilizing	0.001	N	0.159	neutral	N	0.422379194	None	None	N
S/C	0.1056	likely_benign	0.0952	benign	-0.329	Destabilizing	0.836	D	0.449	neutral	None	None	None	None	N
S/D	0.5781	likely_pathogenic	0.5189	ambiguous	-0.361	Destabilizing	0.129	N	0.354	neutral	None	None	None	None	N
S/E	0.7425	likely_pathogenic	0.6907	pathogenic	-0.276	Destabilizing	0.228	N	0.353	neutral	None	None	None	None	N
S/F	0.3446	ambiguous	0.3035	benign	-0.565	Destabilizing	0.836	D	0.445	neutral	None	None	None	None	N
S/G	0.1378	likely_benign	0.1298	benign	-0.857	Destabilizing	0.129	N	0.345	neutral	None	None	None	None	N
S/H	0.5004	ambiguous	0.4347	ambiguous	-1.286	Destabilizing	0.836	D	0.455	neutral	None	None	None	None	N
S/I	0.2622	likely_benign	0.2379	benign	0.248	Stabilizing	0.264	N	0.433	neutral	None	None	None	None	N
S/K	0.8527	likely_pathogenic	0.8085	pathogenic	-0.5	Destabilizing	0.228	N	0.358	neutral	None	None	None	None	N
S/L	0.1363	likely_benign	0.1258	benign	0.248	Stabilizing	0.101	N	0.385	neutral	N	0.511267615	None	None	N
S/M	0.2537	likely_benign	0.2306	benign	0.23	Stabilizing	0.836	D	0.457	neutral	None	None	None	None	N
S/N	0.2006	likely_benign	0.1789	benign	-0.746	Destabilizing	0.004	N	0.178	neutral	None	None	None	None	N
S/P	0.8369	likely_pathogenic	0.7868	pathogenic	0.025	Stabilizing	0.523	D	0.425	neutral	N	0.50524572	None	None	N
S/Q	0.6782	likely_pathogenic	0.6163	pathogenic	-0.641	Destabilizing	0.593	D	0.476	neutral	None	None	None	None	N
S/R	0.8103	likely_pathogenic	0.7654	pathogenic	-0.641	Destabilizing	0.418	N	0.429	neutral	None	None	None	None	N
S/T	0.0785	likely_benign	0.0736	benign	-0.592	Destabilizing	None	N	0.165	neutral	N	0.397075318	None	None	N
S/V	0.2629	likely_benign	0.2297	benign	0.025	Stabilizing	0.129	N	0.389	neutral	None	None	None	None	N
S/W	0.5347	ambiguous	0.4914	ambiguous	-0.733	Destabilizing	0.983	D	0.529	neutral	None	None	None	None	N
S/Y	0.2881	likely_benign	0.2583	benign	-0.357	Destabilizing	0.836	D	0.455	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.