ClinVar Miner

Submissions for variant NM_182914.3(SYNE2):c.12614C>T (p.Thr4205Ile)

gnomAD frequency: 0.00006  dbSNP: rs376207235
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000699066 SCV000387485 benign Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000699066 SCV000827761 uncertain significance Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 4205 of the SYNE2 protein (p.Thr4205Ile). This variant is present in population databases (rs376207235, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SYNE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 313577). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics RCV001288052 SCV001474871 uncertain significance not provided 2020-06-09 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000699066 SCV003820798 likely benign Emery-Dreifuss muscular dystrophy 5, autosomal dominant 2023-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV004021591 SCV003943803 uncertain significance not specified 2023-05-05 criteria provided, single submitter clinical testing The c.12614C>T (p.T4205I) alteration is located in exon 66 (coding exon 65) of the SYNE2 gene. This alteration results from a C to T substitution at nucleotide position 12614, causing the threonine (T) at amino acid position 4205 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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