TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35289	106090;106091;106092	chr2:178530750;178530749;178530748	chr2:179395477;179395476;179395475
N2AB	33648	101167;101168;101169	chr2:178530750;178530749;178530748	chr2:179395477;179395476;179395475
N2A	32721	98386;98387;98388	chr2:178530750;178530749;178530748	chr2:179395477;179395476;179395475
N2B	26224	78895;78896;78897	chr2:178530750;178530749;178530748	chr2:179395477;179395476;179395475
Novex-1	26349	79270;79271;79272	chr2:178530750;178530749;178530748	chr2:179395477;179395476;179395475
Novex-2	26416	79471;79472;79473	chr2:178530750;178530749;178530748	chr2:179395477;179395476;179395475
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-165
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.433
• 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	rs1381430946	-0.78	None	N	0.108	0.048	0.0666544352282	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
T/A	rs1381430946	-0.78	None	N	0.108	0.048	0.0666544352282	gnomAD-4.0.0	3.18195E-06	None	None	None	None	N	None	0	4.57331E-05	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
T/A	0.0886	likely_benign	0.0942	benign	-0.613	Destabilizing	None	N	0.108	neutral	N	0.44204336	None	None	N
T/C	0.3384	likely_benign	0.3863	ambiguous	-0.492	Destabilizing	0.177	N	0.337	neutral	None	None	None	None	N
T/D	0.316	likely_benign	0.3493	ambiguous	-0.071	Destabilizing	0.015	N	0.293	neutral	None	None	None	None	N
T/E	0.2629	likely_benign	0.2823	benign	-0.055	Destabilizing	0.006	N	0.265	neutral	None	None	None	None	N
T/F	0.192	likely_benign	0.2084	benign	-0.607	Destabilizing	0.029	N	0.381	neutral	None	None	None	None	N
T/G	0.2149	likely_benign	0.2542	benign	-0.88	Destabilizing	0.006	N	0.255	neutral	None	None	None	None	N
T/H	0.2024	likely_benign	0.224	benign	-1.104	Destabilizing	0.177	N	0.387	neutral	None	None	None	None	N
T/I	0.1115	likely_benign	0.1149	benign	0.007	Stabilizing	None	N	0.137	neutral	N	0.412523907	None	None	N
T/K	0.1706	likely_benign	0.1844	benign	-0.712	Destabilizing	None	N	0.179	neutral	None	None	None	None	N
T/L	0.0856	likely_benign	0.0915	benign	0.007	Stabilizing	None	N	0.137	neutral	None	None	None	None	N
T/M	0.1014	likely_benign	0.1032	benign	0.03	Stabilizing	0.096	N	0.38	neutral	None	None	None	None	N
T/N	0.1052	likely_benign	0.1163	benign	-0.705	Destabilizing	0.011	N	0.205	neutral	N	0.48708038	None	None	N
T/P	0.1379	likely_benign	0.171	benign	-0.166	Destabilizing	0.022	N	0.344	neutral	N	0.443057318	None	None	N
T/Q	0.1995	likely_benign	0.2169	benign	-0.775	Destabilizing	0.029	N	0.355	neutral	None	None	None	None	N
T/R	0.1371	likely_benign	0.1485	benign	-0.523	Destabilizing	0.015	N	0.285	neutral	None	None	None	None	N
T/S	0.0949	likely_benign	0.1064	benign	-0.951	Destabilizing	None	N	0.164	neutral	N	0.460104423	None	None	N
T/V	0.1205	likely_benign	0.1271	benign	-0.166	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
T/W	0.5265	ambiguous	0.5832	pathogenic	-0.614	Destabilizing	0.712	D	0.418	neutral	None	None	None	None	N
T/Y	0.2455	likely_benign	0.2684	benign	-0.363	Destabilizing	0.177	N	0.469	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.