TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23184	69775;69776;69777	chr2:178576694;178576693;178576692	chr2:179441421;179441420;179441419
N2AB	21543	64852;64853;64854	chr2:178576694;178576693;178576692	chr2:179441421;179441420;179441419
N2A	20616	62071;62072;62073	chr2:178576694;178576693;178576692	chr2:179441421;179441420;179441419
N2B	14119	42580;42581;42582	chr2:178576694;178576693;178576692	chr2:179441421;179441420;179441419
Novex-1	14244	42955;42956;42957	chr2:178576694;178576693;178576692	chr2:179441421;179441420;179441419
Novex-2	14311	43156;43157;43158	chr2:178576694;178576693;178576692	chr2:179441421;179441420;179441419
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-56
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.7514
• 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
L/P	rs1334258779	-0.453	0.939	N	0.275	0.287	0.603223074362	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/P	rs1334258779	-0.453	0.939	N	0.275	0.287	0.603223074362	gnomAD-4.0.0	3.18326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86582E-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
L/A	0.2248	likely_benign	0.2204	benign	-0.425	Destabilizing	0.373	N	0.291	neutral	None	None	None	None	N
L/C	0.5474	ambiguous	0.5765	pathogenic	-0.806	Destabilizing	0.996	D	0.245	neutral	None	None	None	None	N
L/D	0.738	likely_pathogenic	0.7154	pathogenic	-0.009	Destabilizing	0.91	D	0.284	neutral	None	None	None	None	N
L/E	0.4868	ambiguous	0.4742	ambiguous	-0.094	Destabilizing	0.59	D	0.267	neutral	None	None	None	None	N
L/F	0.1794	likely_benign	0.172	benign	-0.569	Destabilizing	0.91	D	0.217	neutral	None	None	None	None	N
L/G	0.3754	ambiguous	0.3893	ambiguous	-0.518	Destabilizing	0.59	D	0.277	neutral	None	None	None	None	N
L/H	0.2909	likely_benign	0.2904	benign	0.105	Stabilizing	0.987	D	0.279	neutral	None	None	None	None	N
L/I	0.1082	likely_benign	0.1066	benign	-0.295	Destabilizing	0.373	N	0.255	neutral	None	None	None	None	N
L/K	0.3689	ambiguous	0.3671	ambiguous	-0.274	Destabilizing	0.009	N	0.217	neutral	None	None	None	None	N
L/M	0.1166	likely_benign	0.1136	benign	-0.591	Destabilizing	0.078	N	0.205	neutral	N	0.399288903	None	None	N
L/N	0.331	likely_benign	0.3296	benign	-0.151	Destabilizing	0.91	D	0.285	neutral	None	None	None	None	N
L/P	0.1882	likely_benign	0.1974	benign	-0.312	Destabilizing	0.939	D	0.275	neutral	N	0.44798414	None	None	N
L/Q	0.1682	likely_benign	0.1732	benign	-0.296	Destabilizing	0.884	D	0.269	neutral	N	0.441095454	None	None	N
L/R	0.2903	likely_benign	0.2917	benign	0.135	Stabilizing	0.792	D	0.26	neutral	N	0.449928368	None	None	N
L/S	0.2395	likely_benign	0.2315	benign	-0.569	Destabilizing	0.037	N	0.216	neutral	None	None	None	None	N
L/T	0.1971	likely_benign	0.1941	benign	-0.553	Destabilizing	0.59	D	0.239	neutral	None	None	None	None	N
L/V	0.1002	likely_benign	0.0986	benign	-0.312	Destabilizing	0.007	N	0.203	neutral	N	0.422915125	None	None	N
L/W	0.3285	likely_benign	0.3271	benign	-0.587	Destabilizing	0.996	D	0.325	neutral	None	None	None	None	N
L/Y	0.4204	ambiguous	0.4158	ambiguous	-0.358	Destabilizing	0.953	D	0.231	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.