TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32989	99190;99191;99192	chr2:178538970;178538969;178538968	chr2:179403697;179403696;179403695
N2AB	31348	94267;94268;94269	chr2:178538970;178538969;178538968	chr2:179403697;179403696;179403695
N2A	30421	91486;91487;91488	chr2:178538970;178538969;178538968	chr2:179403697;179403696;179403695
N2B	23924	71995;71996;71997	chr2:178538970;178538969;178538968	chr2:179403697;179403696;179403695
Novex-1	24049	72370;72371;72372	chr2:178538970;178538969;178538968	chr2:179403697;179403696;179403695
Novex-2	24116	72571;72572;72573	chr2:178538970;178538969;178538968	chr2:179403697;179403696;179403695
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-128
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.4293
• 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	rs779521662	-0.647	0.702	N	0.523	0.226	0.233150807113	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
P/A	rs779521662	-0.647	0.702	N	0.523	0.226	0.233150807113	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/A	rs779521662	-0.647	0.702	N	0.523	0.226	0.233150807113	gnomAD-4.0.0	6.57384E-06	None	None	None	None	N	None	2.41383E-05	0	None	0	0	None	0	0	0	0	0
P/L	rs757583081	-0.214	0.958	N	0.729	0.371	0.675014312329	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.69E-05	0
P/L	rs757583081	-0.214	0.958	N	0.729	0.371	0.675014312329	gnomAD-4.0.0	2.95234E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.79186E-05	0	1.66362E-05
P/R	None	None	0.988	N	0.759	0.385	0.558188439259	gnomAD-4.0.0	6.86591E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02824E-07	0	0
P/S	rs779521662	None	0.157	N	0.305	0.237	0.177238962908	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	1.0018E-04	0	None	0	None	0	0	0
P/S	rs779521662	None	0.157	N	0.305	0.237	0.177238962908	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	5.77034E-04	0	None	0	0	0	0	0
P/S	rs779521662	None	0.157	N	0.305	0.237	0.177238962908	gnomAD-4.0.0	3.86311E-06	None	None	None	None	N	None	0	0	None	1.23062E-04	0	None	0	0	0	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	0.065	likely_benign	0.0676	benign	-0.956	Destabilizing	0.702	D	0.523	neutral	N	0.487790535	None	None	N
P/C	0.5172	ambiguous	0.4977	ambiguous	-0.694	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
P/D	0.532	ambiguous	0.5083	ambiguous	-0.82	Destabilizing	0.938	D	0.617	neutral	None	None	None	None	N
P/E	0.382	ambiguous	0.3645	ambiguous	-0.919	Destabilizing	0.938	D	0.612	neutral	None	None	None	None	N
P/F	0.5724	likely_pathogenic	0.5576	ambiguous	-1.012	Destabilizing	0.997	D	0.847	deleterious	None	None	None	None	N
P/G	0.3326	likely_benign	0.3295	benign	-1.147	Destabilizing	0.938	D	0.617	neutral	None	None	None	None	N
P/H	0.2721	likely_benign	0.2614	benign	-0.643	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
P/I	0.2976	likely_benign	0.2899	benign	-0.581	Destabilizing	0.991	D	0.818	deleterious	None	None	None	None	N
P/K	0.3724	ambiguous	0.3513	ambiguous	-0.808	Destabilizing	0.938	D	0.621	neutral	None	None	None	None	N
P/L	0.1318	likely_benign	0.1323	benign	-0.581	Destabilizing	0.958	D	0.729	deleterious	N	0.515361139	None	None	N
P/M	0.2942	likely_benign	0.3053	benign	-0.396	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
P/N	0.3266	likely_benign	0.3309	benign	-0.499	Destabilizing	0.981	D	0.673	prob.neutral	None	None	None	None	N
P/Q	0.223	likely_benign	0.2161	benign	-0.794	Destabilizing	0.988	D	0.639	neutral	N	0.467695027	None	None	N
P/R	0.2634	likely_benign	0.2453	benign	-0.173	Destabilizing	0.988	D	0.759	deleterious	N	0.473126304	None	None	N
P/S	0.1375	likely_benign	0.1366	benign	-0.896	Destabilizing	0.157	N	0.305	neutral	N	0.484115512	None	None	N
P/T	0.1032	likely_benign	0.1044	benign	-0.898	Destabilizing	0.851	D	0.554	neutral	N	0.519228163	None	None	N
P/V	0.1878	likely_benign	0.1874	benign	-0.671	Destabilizing	0.991	D	0.672	prob.neutral	None	None	None	None	N
P/W	0.7657	likely_pathogenic	0.7337	pathogenic	-1.079	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
P/Y	0.5402	ambiguous	0.5279	ambiguous	-0.809	Destabilizing	0.997	D	0.847	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.