Submissions for variant NM_001267550.2(TTN):c.107163_107167del (p.Phe35721fs)

dbSNP: rs794727544

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000177506	SCV000229384	likely pathogenic	not provided	2015-05-15	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001004966	SCV001164505	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-12-03	criteria provided, single submitter	research	The heterozygous p.Phe35721LeufsTer2 variant in TTN was identified by our study in the compound heterozygous state, with another pathogenic variant, in one individual with limb-girdle muscular dystrophy (LGMD). The presence of this variant in combination with a pathogenic variant and in an individual with LGMD increases the likelihood that the p.Phe35721LeufsTer2 variant is pathogenic. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 35721 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the TTN gene is an established disease mechanism in autosomal recessive LGMD. In summary, this variant meets criteria to be classified as pathogenic for LGMD in an autosomal recessive manner based on the predicted impact of the variant and the presence of a pathogenic variant in an individual with LGMD. ACMG/AMP Criteria applied: PM2, PVS1, PM3 (Richards 2015).
CeGaT Center for Human Genetics Tuebingen	RCV000177506	SCV001962317	pathogenic	not provided	2022-07-01	criteria provided, single submitter	clinical testing