TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18133	54622;54623;54624	chr2:178604290;178604289;178604288	chr2:179469017;179469016;179469015
N2AB	16492	49699;49700;49701	chr2:178604290;178604289;178604288	chr2:179469017;179469016;179469015
N2A	15565	46918;46919;46920	chr2:178604290;178604289;178604288	chr2:179469017;179469016;179469015
N2B	9068	27427;27428;27429	chr2:178604290;178604289;178604288	chr2:179469017;179469016;179469015
Novex-1	9193	27802;27803;27804	chr2:178604290;178604289;178604288	chr2:179469017;179469016;179469015
Novex-2	9260	28003;28004;28005	chr2:178604290;178604289;178604288	chr2:179469017;179469016;179469015
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-19
• Domain position: 69
• Structural Position: 99
• Q(SASA): 0.314
• 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
P/L	None	None	0.669	N	0.413	0.435	0.577797438266	gnomAD-4.0.0	2.08359E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.78673E-05
P/S	rs532354607	None	0.454	N	0.346	0.27	0.301789629655	gnomAD-4.0.0	2.10634E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.66666E-06	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
P/A	0.1066	likely_benign	0.1057	benign	-1.052	Destabilizing	0.454	N	0.363	neutral	N	0.472067013	None	None	N
P/C	0.6362	likely_pathogenic	0.6306	pathogenic	-0.732	Destabilizing	0.998	D	0.523	neutral	None	None	None	None	N
P/D	0.7148	likely_pathogenic	0.741	pathogenic	-0.931	Destabilizing	0.842	D	0.419	neutral	None	None	None	None	N
P/E	0.3919	ambiguous	0.3934	ambiguous	-1.024	Destabilizing	0.842	D	0.399	neutral	None	None	None	None	N
P/F	0.7693	likely_pathogenic	0.7854	pathogenic	-1.078	Destabilizing	0.974	D	0.538	neutral	None	None	None	None	N
P/G	0.3903	ambiguous	0.4258	ambiguous	-1.25	Destabilizing	0.842	D	0.425	neutral	None	None	None	None	N
P/H	0.353	ambiguous	0.3494	ambiguous	-0.73	Destabilizing	0.997	D	0.467	neutral	N	0.486532612	None	None	N
P/I	0.4724	ambiguous	0.4858	ambiguous	-0.655	Destabilizing	0.949	D	0.564	neutral	None	None	None	None	N
P/K	0.3411	ambiguous	0.3474	ambiguous	-0.893	Destabilizing	0.842	D	0.401	neutral	None	None	None	None	N
P/L	0.2398	likely_benign	0.2301	benign	-0.655	Destabilizing	0.669	D	0.413	neutral	N	0.486279122	None	None	N
P/M	0.4911	ambiguous	0.479	ambiguous	-0.441	Destabilizing	0.991	D	0.474	neutral	None	None	None	None	N
P/N	0.4714	ambiguous	0.4892	ambiguous	-0.597	Destabilizing	0.842	D	0.481	neutral	None	None	None	None	N
P/Q	0.2088	likely_benign	0.2077	benign	-0.893	Destabilizing	0.974	D	0.453	neutral	None	None	None	None	N
P/R	0.2408	likely_benign	0.2366	benign	-0.241	Destabilizing	0.934	D	0.493	neutral	D	0.527019006	None	None	N
P/S	0.1875	likely_benign	0.1936	benign	-0.994	Destabilizing	0.454	N	0.346	neutral	N	0.494714587	None	None	N
P/T	0.1436	likely_benign	0.1354	benign	-0.992	Destabilizing	0.007	N	0.131	neutral	N	0.492829075	None	None	N
P/V	0.3148	likely_benign	0.3194	benign	-0.752	Destabilizing	0.728	D	0.356	neutral	None	None	None	None	N
P/W	0.838	likely_pathogenic	0.8497	pathogenic	-1.147	Destabilizing	0.998	D	0.557	neutral	None	None	None	None	N
P/Y	0.6872	likely_pathogenic	0.711	pathogenic	-0.884	Destabilizing	0.991	D	0.538	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.