TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14680	44263;44264;44265	chr2:178630920;178630919;178630918	chr2:179495647;179495646;179495645
N2AB	13039	39340;39341;39342	chr2:178630920;178630919;178630918	chr2:179495647;179495646;179495645
N2A	12112	36559;36560;36561	chr2:178630920;178630919;178630918	chr2:179495647;179495646;179495645
N2B	5615	17068;17069;17070	chr2:178630920;178630919;178630918	chr2:179495647;179495646;179495645
Novex-1	5740	17443;17444;17445	chr2:178630920;178630919;178630918	chr2:179495647;179495646;179495645
Novex-2	5807	17644;17645;17646	chr2:178630920;178630919;178630918	chr2:179495647;179495646;179495645
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: Ig-98
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.3809
• 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/A	None	None	0.856	N	0.756	0.406	0.222439326576	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/L	None	None	0.954	D	0.845	0.337	0.395143324098	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	6.07533E-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
P/A	0.1448	likely_benign	0.1292	benign	-1.005	Destabilizing	0.856	D	0.756	deleterious	N	0.492352789	None	None	N
P/C	0.7191	likely_pathogenic	0.639	pathogenic	-0.518	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
P/D	0.6552	likely_pathogenic	0.5742	pathogenic	-0.771	Destabilizing	0.965	D	0.869	deleterious	None	None	None	None	N
P/E	0.4507	ambiguous	0.3999	ambiguous	-0.849	Destabilizing	0.965	D	0.774	deleterious	None	None	None	None	N
P/F	0.7223	likely_pathogenic	0.6206	pathogenic	-0.967	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
P/G	0.4539	ambiguous	0.4182	ambiguous	-1.226	Destabilizing	0.965	D	0.757	deleterious	None	None	None	None	N
P/H	0.2724	likely_benign	0.2306	benign	-0.781	Destabilizing	0.994	D	0.855	deleterious	N	0.454682987	None	None	N
P/I	0.5792	likely_pathogenic	0.5004	ambiguous	-0.539	Destabilizing	0.982	D	0.892	deleterious	None	None	None	None	N
P/K	0.4105	ambiguous	0.4034	ambiguous	-0.835	Destabilizing	0.797	D	0.813	deleterious	None	None	None	None	N
P/L	0.2279	likely_benign	0.1745	benign	-0.539	Destabilizing	0.954	D	0.845	deleterious	D	0.55497792	None	None	N
P/M	0.548	ambiguous	0.4802	ambiguous	-0.332	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
P/N	0.4943	ambiguous	0.4334	ambiguous	-0.446	Destabilizing	0.965	D	0.865	deleterious	None	None	None	None	N
P/Q	0.2303	likely_benign	0.2148	benign	-0.703	Destabilizing	0.965	D	0.864	deleterious	None	None	None	None	N
P/R	0.2466	likely_benign	0.2335	benign	-0.249	Destabilizing	0.041	N	0.507	neutral	N	0.515198667	None	None	N
P/S	0.224	likely_benign	0.1776	benign	-0.858	Destabilizing	0.954	D	0.749	deleterious	N	0.513340396	None	None	N
P/T	0.2059	likely_benign	0.1723	benign	-0.841	Destabilizing	0.954	D	0.809	deleterious	N	0.515198667	None	None	N
P/V	0.4223	ambiguous	0.366	ambiguous	-0.659	Destabilizing	0.965	D	0.853	deleterious	None	None	None	None	N
P/W	0.8386	likely_pathogenic	0.76	pathogenic	-1.08	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
P/Y	0.6324	likely_pathogenic	0.5384	ambiguous	-0.812	Destabilizing	0.998	D	0.874	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.