TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22425	67498;67499;67500	chr2:178580014;178580013;178580012	chr2:179444741;179444740;179444739
N2AB	20784	62575;62576;62577	chr2:178580014;178580013;178580012	chr2:179444741;179444740;179444739
N2A	19857	59794;59795;59796	chr2:178580014;178580013;178580012	chr2:179444741;179444740;179444739
N2B	13360	40303;40304;40305	chr2:178580014;178580013;178580012	chr2:179444741;179444740;179444739
Novex-1	13485	40678;40679;40680	chr2:178580014;178580013;178580012	chr2:179444741;179444740;179444739
Novex-2	13552	40879;40880;40881	chr2:178580014;178580013;178580012	chr2:179444741;179444740;179444739
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-50
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1857
• 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
F/S	None	None	0.815	N	0.544	0.369	0.697227279014	gnomAD-4.0.0	3.18457E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86599E-05	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
F/A	0.8132	likely_pathogenic	0.7642	pathogenic	-2.423	Highly Destabilizing	0.543	D	0.566	neutral	None	None	None	None	N
F/C	0.3479	ambiguous	0.3287	benign	-1.095	Destabilizing	0.007	N	0.514	neutral	N	0.4798272	None	None	N
F/D	0.9592	likely_pathogenic	0.9507	pathogenic	-2.297	Highly Destabilizing	0.984	D	0.629	neutral	None	None	None	None	N
F/E	0.9646	likely_pathogenic	0.9497	pathogenic	-2.119	Highly Destabilizing	0.953	D	0.627	neutral	None	None	None	None	N
F/G	0.9116	likely_pathogenic	0.8867	pathogenic	-2.816	Highly Destabilizing	0.854	D	0.585	neutral	None	None	None	None	N
F/H	0.6461	likely_pathogenic	0.5737	pathogenic	-1.277	Destabilizing	0.91	D	0.563	neutral	None	None	None	None	N
F/I	0.5002	ambiguous	0.4184	ambiguous	-1.163	Destabilizing	0.684	D	0.533	neutral	N	0.474824025	None	None	N
F/K	0.9414	likely_pathogenic	0.9226	pathogenic	-1.298	Destabilizing	0.953	D	0.613	neutral	None	None	None	None	N
F/L	0.924	likely_pathogenic	0.8999	pathogenic	-1.163	Destabilizing	0.309	N	0.573	neutral	N	0.479499126	None	None	N
F/M	0.7685	likely_pathogenic	0.7015	pathogenic	-0.867	Destabilizing	0.984	D	0.541	neutral	None	None	None	None	N
F/N	0.7941	likely_pathogenic	0.7511	pathogenic	-1.629	Destabilizing	0.953	D	0.624	neutral	None	None	None	None	N
F/P	0.9985	likely_pathogenic	0.9984	pathogenic	-1.589	Destabilizing	0.984	D	0.649	neutral	None	None	None	None	N
F/Q	0.8819	likely_pathogenic	0.841	pathogenic	-1.633	Destabilizing	0.953	D	0.649	neutral	None	None	None	None	N
F/R	0.849	likely_pathogenic	0.8196	pathogenic	-0.85	Destabilizing	0.953	D	0.633	neutral	None	None	None	None	N
F/S	0.6713	likely_pathogenic	0.5938	pathogenic	-2.287	Highly Destabilizing	0.815	D	0.544	neutral	N	0.474802595	None	None	N
F/T	0.7839	likely_pathogenic	0.7169	pathogenic	-2.013	Highly Destabilizing	0.854	D	0.567	neutral	None	None	None	None	N
F/V	0.4507	ambiguous	0.3865	ambiguous	-1.589	Destabilizing	0.684	D	0.55	neutral	N	0.471186287	None	None	N
F/W	0.6379	likely_pathogenic	0.6049	pathogenic	-0.106	Destabilizing	0.953	D	0.565	neutral	None	None	None	None	N
F/Y	0.0811	likely_benign	0.0825	benign	-0.409	Destabilizing	0.007	N	0.294	neutral	N	0.394555087	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.