TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1116	3571;3572;3573	chr2:178782246;178782245;178782244	chr2:179646973;179646972;179646971
N2AB	1116	3571;3572;3573	chr2:178782246;178782245;178782244	chr2:179646973;179646972;179646971
N2A	1116	3571;3572;3573	chr2:178782246;178782245;178782244	chr2:179646973;179646972;179646971
N2B	1070	3433;3434;3435	chr2:178782246;178782245;178782244	chr2:179646973;179646972;179646971
Novex-1	1070	3433;3434;3435	chr2:178782246;178782245;178782244	chr2:179646973;179646972;179646971
Novex-2	1070	3433;3434;3435	chr2:178782246;178782245;178782244	chr2:179646973;179646972;179646971
Novex-3	1116	3571;3572;3573	chr2:178782246;178782245;178782244	chr2:179646973;179646972;179646971

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-4
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1872
• 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
K/E	rs1254035556	None	0.999	N	0.587	0.399	0.258779203287	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92308E-04	None	0	0	0	0	0
K/E	rs1254035556	None	0.999	N	0.587	0.399	0.258779203287	gnomAD-4.0.0	6.57108E-06	None	None	None	None	N	None	0	0	None	0	1.92308E-04	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
K/A	0.9664	likely_pathogenic	0.9575	pathogenic	-1.264	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
K/C	0.9683	likely_pathogenic	0.9542	pathogenic	-1.367	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/D	0.995	likely_pathogenic	0.9932	pathogenic	-1.324	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/E	0.8679	likely_pathogenic	0.8201	pathogenic	-1.072	Destabilizing	0.999	D	0.587	neutral	N	0.449946307	None	None	N
K/F	0.9801	likely_pathogenic	0.9744	pathogenic	-0.658	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
K/G	0.9723	likely_pathogenic	0.966	pathogenic	-1.715	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/H	0.8316	likely_pathogenic	0.7946	pathogenic	-1.893	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
K/I	0.8901	likely_pathogenic	0.8541	pathogenic	-0.014	Destabilizing	1.0	D	0.788	deleterious	N	0.449024248	None	None	N
K/L	0.8058	likely_pathogenic	0.7664	pathogenic	-0.014	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/M	0.6438	likely_pathogenic	0.5799	pathogenic	-0.372	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/N	0.9626	likely_pathogenic	0.9493	pathogenic	-1.442	Destabilizing	1.0	D	0.751	deleterious	N	0.449306925	None	None	N
K/P	0.9993	likely_pathogenic	0.9992	pathogenic	-0.407	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/Q	0.5048	ambiguous	0.435	ambiguous	-1.208	Destabilizing	1.0	D	0.747	deleterious	N	0.443788618	None	None	N
K/R	0.1769	likely_benign	0.1579	benign	-0.98	Destabilizing	0.999	D	0.538	neutral	N	0.445571559	None	None	N
K/S	0.9662	likely_pathogenic	0.9539	pathogenic	-2.024	Highly Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/T	0.8037	likely_pathogenic	0.7626	pathogenic	-1.529	Destabilizing	1.0	D	0.739	prob.delet.	N	0.428805572	None	None	N
K/V	0.8585	likely_pathogenic	0.826	pathogenic	-0.407	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/W	0.9765	likely_pathogenic	0.9693	pathogenic	-0.674	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Y	0.9342	likely_pathogenic	0.918	pathogenic	-0.302	Destabilizing	1.0	D	0.779	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.