Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000232366 | SCV000286385 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-12-07 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000593827 | SCV000707076 | uncertain significance | not provided | 2017-03-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000593827 | SCV000984984 | uncertain significance | not provided | 2023-03-15 | criteria provided, single submitter | clinical testing | Observed with a nonsense variant on the same allele (in cis) in an individual referred for genetic testing at GeneDx who harbored a second nonsense variant suspected to be on the opposite allele (in trans) based on familial testing; Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; This variant is associated with the following publications: (PMID: 23975875, 30665247) |
Ce |
RCV000593827 | SCV001152604 | uncertain significance | not provided | 2018-08-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174795 | SCV001338139 | uncertain significance | not specified | 2020-02-03 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.92992A>G (p.Thr30998Ala) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 238290 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.92992A>G has been reported in the literature in one individual affected with Titinopathy/congenital fiber type disproportion. However, co-occurrence with another pathogenic variant has been reported in this patient (TTN c.72880delA / p.S24294fs), providing supporting evidence for a benign role (Waldrop_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (2x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |