TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28816	86671;86672;86673	chr2:178559686;178559685;178559684	chr2:179424413;179424412;179424411
N2AB	27175	81748;81749;81750	chr2:178559686;178559685;178559684	chr2:179424413;179424412;179424411
N2A	26248	78967;78968;78969	chr2:178559686;178559685;178559684	chr2:179424413;179424412;179424411
N2B	19751	59476;59477;59478	chr2:178559686;178559685;178559684	chr2:179424413;179424412;179424411
Novex-1	19876	59851;59852;59853	chr2:178559686;178559685;178559684	chr2:179424413;179424412;179424411
Novex-2	19943	60052;60053;60054	chr2:178559686;178559685;178559684	chr2:179424413;179424412;179424411
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-144
• Domain position: 62
• Structural Position: 145
• Q(SASA): 0.5714
• 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
N/K	rs774349799	0.146	0.324	N	0.237	0.189	0.232513804876	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
N/K	rs774349799	0.146	0.324	N	0.237	0.189	0.232513804876	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.2068E-04	0	0	0	0	None	0	0	0	0	0
N/K	rs774349799	0.146	0.324	N	0.237	0.189	0.232513804876	gnomAD-4.0.0	3.72583E-06	None	None	None	None	N	None	8.01967E-05	0	None	0	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
N/A	0.1897	likely_benign	0.1821	benign	-0.485	Destabilizing	0.116	N	0.34	neutral	None	None	None	None	N
N/C	0.1973	likely_benign	0.1948	benign	0.293	Stabilizing	0.981	D	0.425	neutral	None	None	None	None	N
N/D	0.0894	likely_benign	0.1022	benign	-0.834	Destabilizing	0.324	N	0.263	neutral	D	0.523149195	None	None	N
N/E	0.3729	ambiguous	0.3883	ambiguous	-0.832	Destabilizing	0.241	N	0.237	neutral	None	None	None	None	N
N/F	0.4885	ambiguous	0.4742	ambiguous	-0.721	Destabilizing	0.69	D	0.429	neutral	None	None	None	None	N
N/G	0.1962	likely_benign	0.1906	benign	-0.716	Destabilizing	0.207	N	0.241	neutral	None	None	None	None	N
N/H	0.1199	likely_benign	0.1197	benign	-0.787	Destabilizing	0.003	N	0.229	neutral	D	0.530288598	None	None	N
N/I	0.2661	likely_benign	0.2455	benign	0.056	Stabilizing	0.457	N	0.408	neutral	N	0.495531832	None	None	N
N/K	0.3251	likely_benign	0.3425	ambiguous	-0.08	Destabilizing	0.324	N	0.237	neutral	N	0.501829773	None	None	N
N/L	0.2117	likely_benign	0.2037	benign	0.056	Stabilizing	0.241	N	0.368	neutral	None	None	None	None	N
N/M	0.2887	likely_benign	0.2819	benign	0.728	Stabilizing	0.944	D	0.395	neutral	None	None	None	None	N
N/P	0.821	likely_pathogenic	0.8065	pathogenic	-0.097	Destabilizing	0.818	D	0.369	neutral	None	None	None	None	N
N/Q	0.3192	likely_benign	0.3226	benign	-0.808	Destabilizing	0.69	D	0.342	neutral	None	None	None	None	N
N/R	0.3637	ambiguous	0.38	ambiguous	0.068	Stabilizing	0.388	N	0.302	neutral	None	None	None	None	N
N/S	0.0601	likely_benign	0.0612	benign	-0.435	Destabilizing	0.09	N	0.322	neutral	N	0.469912143	None	None	N
N/T	0.075	likely_benign	0.08	benign	-0.289	Destabilizing	None	N	0.123	neutral	N	0.446843282	None	None	N
N/V	0.2135	likely_benign	0.1989	benign	-0.097	Destabilizing	0.241	N	0.375	neutral	None	None	None	None	N
N/W	0.7847	likely_pathogenic	0.7803	pathogenic	-0.614	Destabilizing	0.981	D	0.505	neutral	None	None	None	None	N
N/Y	0.2147	likely_benign	0.213	benign	-0.346	Destabilizing	0.457	N	0.391	neutral	N	0.502279782	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.