TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22970	69133;69134;69135	chr2:178577427;178577426;178577425	chr2:179442154;179442153;179442152
N2AB	21329	64210;64211;64212	chr2:178577427;178577426;178577425	chr2:179442154;179442153;179442152
N2A	20402	61429;61430;61431	chr2:178577427;178577426;178577425	chr2:179442154;179442153;179442152
N2B	13905	41938;41939;41940	chr2:178577427;178577426;178577425	chr2:179442154;179442153;179442152
Novex-1	14030	42313;42314;42315	chr2:178577427;178577426;178577425	chr2:179442154;179442153;179442152
Novex-2	14097	42514;42515;42516	chr2:178577427;178577426;178577425	chr2:179442154;179442153;179442152
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-128
• Domain position: 21
• Structural Position: 34
• Q(SASA): 0.1378
• 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/G	None	None	0.994	N	0.525	0.212	0.18274738541	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	0	3.66327E-05

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	0.1005	likely_benign	0.1	benign	-0.258	Destabilizing	0.98	D	0.501	neutral	None	None	None	None	N
S/C	0.1475	likely_benign	0.1474	benign	-0.347	Destabilizing	1.0	D	0.696	prob.neutral	N	0.462502516	None	None	N
S/D	0.4128	ambiguous	0.4219	ambiguous	0.428	Stabilizing	0.996	D	0.603	neutral	None	None	None	None	N
S/E	0.4879	ambiguous	0.5119	ambiguous	0.326	Stabilizing	0.992	D	0.519	neutral	None	None	None	None	N
S/F	0.3536	ambiguous	0.361	ambiguous	-0.936	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
S/G	0.1218	likely_benign	0.1175	benign	-0.327	Destabilizing	0.994	D	0.525	neutral	N	0.503807633	None	None	N
S/H	0.2888	likely_benign	0.2918	benign	-0.724	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
S/I	0.3186	likely_benign	0.3155	benign	-0.213	Destabilizing	0.999	D	0.729	prob.delet.	N	0.458446683	None	None	N
S/K	0.5309	ambiguous	0.5474	ambiguous	-0.304	Destabilizing	0.398	N	0.341	neutral	None	None	None	None	N
S/L	0.1621	likely_benign	0.1638	benign	-0.213	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
S/M	0.2712	likely_benign	0.2701	benign	-0.144	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
S/N	0.1511	likely_benign	0.1432	benign	-0.09	Destabilizing	0.994	D	0.59	neutral	N	0.487011383	None	None	N
S/P	0.8847	likely_pathogenic	0.8493	pathogenic	-0.202	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/Q	0.3991	ambiguous	0.4044	ambiguous	-0.294	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
S/R	0.4251	ambiguous	0.4379	ambiguous	-0.13	Destabilizing	0.978	D	0.677	prob.neutral	N	0.456843192	None	None	N
S/T	0.0951	likely_benign	0.0949	benign	-0.226	Destabilizing	0.994	D	0.524	neutral	N	0.459382065	None	None	N
S/V	0.2962	likely_benign	0.2884	benign	-0.202	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
S/W	0.4651	ambiguous	0.4858	ambiguous	-0.979	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
S/Y	0.2234	likely_benign	0.228	benign	-0.673	Destabilizing	1.0	D	0.741	deleterious	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.