TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23779	71560;71561;71562	chr2:178574797;178574796;178574795	chr2:179439524;179439523;179439522
N2AB	22138	66637;66638;66639	chr2:178574797;178574796;178574795	chr2:179439524;179439523;179439522
N2A	21211	63856;63857;63858	chr2:178574797;178574796;178574795	chr2:179439524;179439523;179439522
N2B	14714	44365;44366;44367	chr2:178574797;178574796;178574795	chr2:179439524;179439523;179439522
Novex-1	14839	44740;44741;44742	chr2:178574797;178574796;178574795	chr2:179439524;179439523;179439522
Novex-2	14906	44941;44942;44943	chr2:178574797;178574796;178574795	chr2:179439524;179439523;179439522
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: Fn3-60
• Domain position: 54
• Structural Position: 70
• Q(SASA): 0.5693
• 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/I	rs1709480973	None	0.549	N	0.357	0.18	0.245660935333	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1709480973	None	0.549	N	0.357	0.18	0.245660935333	gnomAD-4.0.0	4.34229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93807E-06	0	0
T/P	rs1575793122	None	0.712	N	0.348	0.207	0.241078983079	gnomAD-4.0.0	1.30136E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.71038E-05	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	0.0645	likely_benign	0.0602	benign	-0.61	Destabilizing	0.001	N	0.079	neutral	N	0.427974228	None	None	N
T/C	0.4557	ambiguous	0.3969	ambiguous	-0.335	Destabilizing	0.92	D	0.339	neutral	None	None	None	None	N
T/D	0.5454	ambiguous	0.517	ambiguous	-0.273	Destabilizing	0.617	D	0.316	neutral	None	None	None	None	N
T/E	0.4993	ambiguous	0.4625	ambiguous	-0.319	Destabilizing	0.617	D	0.313	neutral	None	None	None	None	N
T/F	0.4894	ambiguous	0.4446	ambiguous	-0.873	Destabilizing	0.92	D	0.385	neutral	None	None	None	None	N
T/G	0.1711	likely_benign	0.1569	benign	-0.812	Destabilizing	0.25	N	0.332	neutral	None	None	None	None	N
T/H	0.3499	ambiguous	0.32	benign	-1.157	Destabilizing	0.92	D	0.325	neutral	None	None	None	None	N
T/I	0.4368	ambiguous	0.366	ambiguous	-0.179	Destabilizing	0.549	D	0.357	neutral	N	0.475669387	None	None	N
T/K	0.3002	likely_benign	0.253	benign	-0.653	Destabilizing	0.447	N	0.315	neutral	None	None	None	None	N
T/L	0.1695	likely_benign	0.1494	benign	-0.179	Destabilizing	0.25	N	0.316	neutral	None	None	None	None	N
T/M	0.1318	likely_benign	0.1169	benign	0.189	Stabilizing	0.972	D	0.339	neutral	None	None	None	None	N
T/N	0.1266	likely_benign	0.1194	benign	-0.477	Destabilizing	0.379	N	0.231	neutral	N	0.459990646	None	None	N
T/P	0.123	likely_benign	0.126	benign	-0.292	Destabilizing	0.712	D	0.348	neutral	N	0.473421303	None	None	N
T/Q	0.2912	likely_benign	0.2649	benign	-0.743	Destabilizing	0.85	D	0.385	neutral	None	None	None	None	N
T/R	0.3069	likely_benign	0.2595	benign	-0.335	Destabilizing	0.617	D	0.355	neutral	None	None	None	None	N
T/S	0.0881	likely_benign	0.0854	benign	-0.701	Destabilizing	0.002	N	0.085	neutral	N	0.388687908	None	None	N
T/V	0.2442	likely_benign	0.2077	benign	-0.292	Destabilizing	0.25	N	0.266	neutral	None	None	None	None	N
T/W	0.8233	likely_pathogenic	0.7835	pathogenic	-0.816	Destabilizing	0.992	D	0.377	neutral	None	None	None	None	N
T/Y	0.4513	ambiguous	0.4195	ambiguous	-0.576	Destabilizing	0.972	D	0.379	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.